Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Microbial Infection and Rheumatoid Arthritis</title><author><name sortKey="Li, Song" sort="Li, Song" uniqKey="Li S" first="Song" last="Li">Song Li</name><affiliation><nlm:aff id="A1">Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation></author><author><name sortKey="Yu, Yangsheng" sort="Yu, Yangsheng" uniqKey="Yu Y" first="Yangsheng" last="Yu">Yangsheng Yu</name><affiliation><nlm:aff id="A1">Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation></author><author><name sortKey="Yue, Yinshi" sort="Yue, Yinshi" uniqKey="Yue Y" first="Yinshi" last="Yue">Yinshi Yue</name><affiliation><nlm:aff id="A1">Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation></author><author><name sortKey="Zhang, Zhixin" sort="Zhang, Zhixin" uniqKey="Zhang Z" first="Zhixin" last="Zhang">Zhixin Zhang</name><affiliation><nlm:aff id="A1">Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation></author><author><name sortKey="Su, Kaihong" sort="Su, Kaihong" uniqKey="Su K" first="Kaihong" last="Su">Kaihong Su</name><affiliation><nlm:aff id="A1">Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25133066</idno><idno type="pmc">4131749</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131749</idno><idno type="RBID">PMC:4131749</idno><idno type="doi">10.4172/2155-9899.1000174</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000785</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000785</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Microbial Infection and Rheumatoid Arthritis</title><author><name sortKey="Li, Song" sort="Li, Song" uniqKey="Li S" first="Song" last="Li">Song Li</name><affiliation><nlm:aff id="A1">Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation></author><author><name sortKey="Yu, Yangsheng" sort="Yu, Yangsheng" uniqKey="Yu Y" first="Yangsheng" last="Yu">Yangsheng Yu</name><affiliation><nlm:aff id="A1">Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation></author><author><name sortKey="Yue, Yinshi" sort="Yue, Yinshi" uniqKey="Yue Y" first="Yinshi" last="Yue">Yinshi Yue</name><affiliation><nlm:aff id="A1">Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation></author><author><name sortKey="Zhang, Zhixin" sort="Zhang, Zhixin" uniqKey="Zhang Z" first="Zhixin" last="Zhang">Zhixin Zhang</name><affiliation><nlm:aff id="A1">Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation></author><author><name sortKey="Su, Kaihong" sort="Su, Kaihong" uniqKey="Su K" first="Kaihong" last="Su">Kaihong Su</name><affiliation><nlm:aff id="A1">Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of clinical & cellular immunology</title><idno type="eISSN">2155-9899</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Rheumatoid arthritis (RA) is a complex autoimmune disease affecting 1–2% of general worldwide population. The etiopathogenesis of RA involves the interplay of multiple genetic risk factors and environmental triggers. Microbial infections are believed to play an important role in the initiation and perpetuation of RA. Recent clinical studies have shown the association of microbial infections with RA. Accumulated studies using animal models have also found that microbial infections can induce and/or exaggerate the symptoms of experimental arthritis. In this review, we have identified the most common microbial infections associated with RA in the literature and summarized the current evidence supporting their pathogenic role in RA. We also discussed the potential mechanisms whereby infection may promote the development of RA, such as generation of neo-autoantigens, induction of loss of tolerance by molecular mimicry, and bystander activation of the immune system.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Scott, Dl" uniqKey="Scott D">DL Scott</name></author><author><name sortKey="Wolfe, F" uniqKey="Wolfe F">F Wolfe</name></author><author><name sortKey="Huizinga, Tw" uniqKey="Huizinga T">TW Huizinga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcinnes, Ib" uniqKey="Mcinnes I">IB McInnes</name></author><author><name sortKey="Schett, G" uniqKey="Schett G">G Schett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hitchon, Ca" uniqKey="Hitchon C">CA Hitchon</name></author><author><name sortKey="El Gabalawy, Hs" uniqKey="El Gabalawy H">HS El-Gabalawy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carty, Sm" uniqKey="Carty S">SM Carty</name></author><author><name sortKey="Snowden, N" uniqKey="Snowden N">N Snowden</name></author><author><name sortKey="Silman, Aj" uniqKey="Silman A">AJ Silman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Silman, Aj" uniqKey="Silman A">AJ Silman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Pablo, P" uniqKey="De Pablo P">P de Pablo</name></author><author><name sortKey="Dietrich, T" uniqKey="Dietrich T">T Dietrich</name></author><author><name sortKey="Mcalindon, Te" uniqKey="Mcalindon T">TE McAlindon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dissick, A" uniqKey="Dissick A">A Dissick</name></author><author><name sortKey="Redman, Rs" uniqKey="Redman R">RS Redman</name></author><author><name sortKey="Jones, M" uniqKey="Jones M">M Jones</name></author><author><name sortKey="Rangan, Bv" uniqKey="Rangan B">BV Rangan</name></author><author><name sortKey="Reimold, A" uniqKey="Reimold A">A Reimold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smit, Md" uniqKey="Smit M">MD Smit</name></author><author><name sortKey="Westra, J" uniqKey="Westra J">J Westra</name></author><author><name sortKey="Vissink, A" uniqKey="Vissink A">A Vissink</name></author><author><name sortKey="Doornbos Van Der Meer, B" uniqKey="Doornbos Van Der Meer B">B Doornbos-van der Meer</name></author><author><name sortKey="Brouwer, E" uniqKey="Brouwer E">E Brouwer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arkema, Ev" uniqKey="Arkema E">EV Arkema</name></author><author><name sortKey="Karlson, Ew" uniqKey="Karlson E">EW Karlson</name></author><author><name sortKey="Costenbader, Kh" uniqKey="Costenbader K">KH Costenbader</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Demmer, Rt" uniqKey="Demmer R">RT Demmer</name></author><author><name sortKey="Molitor, Ja" uniqKey="Molitor J">JA Molitor</name></author><author><name sortKey="Jacobs, Dr" uniqKey="Jacobs D">DR Jacobs</name></author><author><name sortKey="Michalowicz, Bs" uniqKey="Michalowicz B">BS Michalowicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Puntis, D" uniqKey="Puntis D">D Puntis</name></author><author><name sortKey="Malik, S" uniqKey="Malik S">S Malik</name></author><author><name sortKey="Saravanan, V" uniqKey="Saravanan V">V Saravanan</name></author><author><name sortKey="Rynne, M" uniqKey="Rynne M">M Rynne</name></author><author><name sortKey="Heycock, C" uniqKey="Heycock C">C Heycock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Senior, Bw" uniqKey="Senior B">BW Senior</name></author><author><name sortKey="Anderson, Ga" uniqKey="Anderson G">GA Anderson</name></author><author><name sortKey="Morley, Kd" uniqKey="Morley K">KD Morley</name></author><author><name sortKey="Kerr, Ma" uniqKey="Kerr M">MA Kerr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Becker, J" uniqKey="Becker J">J Becker</name></author><author><name sortKey="Winthrop, Kl" uniqKey="Winthrop K">KL Winthrop</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Ell, Jr" uniqKey="O Ell J">JR O’Dell</name></author><author><name sortKey="Blakely, Kw" uniqKey="Blakely K">KW Blakely</name></author><author><name sortKey="Mallek, Ja" uniqKey="Mallek J">JA Mallek</name></author><author><name sortKey="Eckhoff, Pj" uniqKey="Eckhoff P">PJ Eckhoff</name></author><author><name sortKey="Leff, Rd" uniqKey="Leff R">RD Leff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pillemer, S" uniqKey="Pillemer S">S Pillemer</name></author><author><name sortKey="Gulko, P" uniqKey="Gulko P">P Gulko</name></author><author><name sortKey="Ligier, S" uniqKey="Ligier S">S Ligier</name></author><author><name sortKey="Yarboro, C" uniqKey="Yarboro C">C Yarboro</name></author><author><name sortKey="Gourley, M" uniqKey="Gourley M">M Gourley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okada, M" uniqKey="Okada M">M Okada</name></author><author><name sortKey="Kobayashi, T" uniqKey="Kobayashi T">T Kobayashi</name></author><author><name sortKey="Ito, S" uniqKey="Ito S">S Ito</name></author><author><name sortKey="Yokoyama, T" uniqKey="Yokoyama T">T Yokoyama</name></author><author><name sortKey="Abe, A" uniqKey="Abe A">A Abe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martinez Martinez, Re" uniqKey="Martinez Martinez R">RE Martinez-Martinez</name></author><author><name sortKey="Abud Mendoza, C" uniqKey="Abud Mendoza C">C Abud-Mendoza</name></author><author><name sortKey="Pati O Marin, N" uniqKey="Pati O Marin N">N Patiño-Marin</name></author><author><name sortKey="Rizo Rodriguez, Jc" uniqKey="Rizo Rodriguez J">JC Rizo-Rodríguez</name></author><author><name sortKey="Little, Jw" uniqKey="Little J">JW Little</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schaeverbeke, T" uniqKey="Schaeverbeke T">T Schaeverbeke</name></author><author><name sortKey="Renaudin, H" uniqKey="Renaudin H">H Renaudin</name></author><author><name sortKey="Clerc, M" uniqKey="Clerc M">M Clerc</name></author><author><name sortKey="Lequen, L" uniqKey="Lequen L">L Lequen</name></author><author><name sortKey="Vernhes, Jp" uniqKey="Vernhes J">JP Vernhes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoffman, Rw" uniqKey="Hoffman R">RW Hoffman</name></author><author><name sortKey="O Ullivan, Fx" uniqKey="O Ullivan F">FX O’Sullivan</name></author><author><name sortKey="Schafermeyer, Kr" uniqKey="Schafermeyer K">KR Schafermeyer</name></author><author><name sortKey="Moore, Tl" uniqKey="Moore T">TL Moore</name></author><author><name sortKey="Roussell, D" uniqKey="Roussell D">D Roussell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saal, Jg" uniqKey="Saal J">JG Saal</name></author><author><name sortKey="Steidle, M" uniqKey="Steidle M">M Steidle</name></author><author><name sortKey="Einsele, H" uniqKey="Einsele H">H Einsele</name></author><author><name sortKey="Muller, Ca" uniqKey="Muller C">CA Müller</name></author><author><name sortKey="Fritz, P" uniqKey="Fritz P">P Fritz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takeda, T" uniqKey="Takeda T">T Takeda</name></author><author><name sortKey="Mizugaki, Y" uniqKey="Mizugaki Y">Y Mizugaki</name></author><author><name sortKey="Matsubara, L" uniqKey="Matsubara L">L Matsubara</name></author><author><name sortKey="Imai, S" uniqKey="Imai S">S Imai</name></author><author><name sortKey="Koike, T" uniqKey="Koike T">T Koike</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mehraein, Y" uniqKey="Mehraein Y">Y Mehraein</name></author><author><name sortKey="Lennerz, C" uniqKey="Lennerz C">C Lennerz</name></author><author><name sortKey="Ehlhardt, S" uniqKey="Ehlhardt S">S Ehlhardt</name></author><author><name sortKey="Remberger, K" uniqKey="Remberger K">K Remberger</name></author><author><name sortKey="Ojak, A" uniqKey="Ojak A">A Ojak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tamm, A" uniqKey="Tamm A">A Tamm</name></author><author><name sortKey="Ziegler, T" uniqKey="Ziegler T">T Ziegler</name></author><author><name sortKey="Lautenschlager, I" uniqKey="Lautenschlager I">I Lautenschlager</name></author><author><name sortKey="Nikkari, S" uniqKey="Nikkari S">S Nikkari</name></author><author><name sortKey="Mottonen, T" uniqKey="Mottonen T">T Möttönen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Newkirk, Mm" uniqKey="Newkirk M">MM Newkirk</name></author><author><name sortKey="Watanabe Duffy, Kn" uniqKey="Watanabe Duffy K">KN Watanabe Duffy</name></author><author><name sortKey="Leclerc, J" uniqKey="Leclerc J">J Leclerc</name></author><author><name sortKey="Lambert, N" uniqKey="Lambert N">N Lambert</name></author><author><name sortKey="Shiroky, Jb" uniqKey="Shiroky J">JB Shiroky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Nikkari, S" uniqKey="Nikkari S">S Nikkari</name></author><author><name sortKey="Skurnik, M" uniqKey="Skurnik M">M Skurnik</name></author><author><name sortKey="Ziegler, T" uniqKey="Ziegler T">T Ziegler</name></author><author><name sortKey="Luukkainen, R" uniqKey="Luukkainen R">R Luukkainen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Heijden, Im" uniqKey="Van Der Heijden I">IM van der Heijden</name></author><author><name sortKey="Wilbrink, B" uniqKey="Wilbrink B">B Wilbrink</name></author><author><name sortKey="Tchetverikov, I" uniqKey="Tchetverikov I">I Tchetverikov</name></author><author><name sortKey="Schrijver, Ia" uniqKey="Schrijver I">IA Schrijver</name></author><author><name sortKey="Schouls, Lm" uniqKey="Schouls L">LM Schouls</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, T" uniqKey="Chen T">T Chen</name></author><author><name sortKey="Rimpilainen, M" uniqKey="Rimpilainen M">M Rimpilainen</name></author><author><name sortKey="Luukkainen, R" uniqKey="Luukkainen R">R Luukkainen</name></author><author><name sortKey="Mottonen, T" uniqKey="Mottonen T">T Mottonen</name></author><author><name sortKey="Yli Jama, T" uniqKey="Yli Jama T">T Yli-Jama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eerola, E" uniqKey="Eerola E">E Eerola</name></author><author><name sortKey="Mottonen, T" uniqKey="Mottonen T">T Möttönen</name></author><author><name sortKey="Hannonen, P" uniqKey="Hannonen P">P Hannonen</name></author><author><name sortKey="Luukkainen, R" uniqKey="Luukkainen R">R Luukkainen</name></author><author><name sortKey="Kantola, I" uniqKey="Kantola I">I Kantola</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawahito, Y" uniqKey="Kawahito Y">Y Kawahito</name></author><author><name sortKey="Ichinose, S" uniqKey="Ichinose S">S Ichinose</name></author><author><name sortKey="Sano, H" uniqKey="Sano H">H Sano</name></author><author><name sortKey="Tsubouchi, Y" uniqKey="Tsubouchi Y">Y Tsubouchi</name></author><author><name sortKey="Kohno, M" uniqKey="Kohno M">M Kohno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Newkirk, Mm" uniqKey="Newkirk M">MM Newkirk</name></author><author><name sortKey="Goldbach Mansky, R" uniqKey="Goldbach Mansky R">R Goldbach-Mansky</name></author><author><name sortKey="Senior, Bw" uniqKey="Senior B">BW Senior</name></author><author><name sortKey="Klippel, J" uniqKey="Klippel J">J Klippel</name></author><author><name sortKey="Schumacher, Hr" uniqKey="Schumacher H">HR Schumacher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kjeldsen Kragh, J" uniqKey="Kjeldsen Kragh J">J Kjeldsen-Kragh</name></author><author><name sortKey="Rashid, T" uniqKey="Rashid T">T Rashid</name></author><author><name sortKey="Dybwad, A" uniqKey="Dybwad A">A Dybwad</name></author><author><name sortKey="Sioud, M" uniqKey="Sioud M">M Sioud</name></author><author><name sortKey="Haugen, M" uniqKey="Haugen M">M Haugen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tiwana, H" uniqKey="Tiwana H">H Tiwana</name></author><author><name sortKey="Wilson, C" uniqKey="Wilson C">C Wilson</name></author><author><name sortKey="Alvarez, A" uniqKey="Alvarez A">A Alvarez</name></author><author><name sortKey="Abuknesha, R" uniqKey="Abuknesha R">R Abuknesha</name></author><author><name sortKey="Bansal, S" uniqKey="Bansal S">S Bansal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rashid, T" uniqKey="Rashid T">T Rashid</name></author><author><name sortKey="Jayakumar, Ks" uniqKey="Jayakumar K">KS Jayakumar</name></author><author><name sortKey="Binder, A" uniqKey="Binder A">A Binder</name></author><author><name sortKey="Ellis, S" uniqKey="Ellis S">S Ellis</name></author><author><name sortKey="Cunningham, P" uniqKey="Cunningham P">P Cunningham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hitchon, Ca" uniqKey="Hitchon C">CA Hitchon</name></author><author><name sortKey="Chandad, F" uniqKey="Chandad F">F Chandad</name></author><author><name sortKey="Ferucci, Ed" uniqKey="Ferucci E">ED Ferucci</name></author><author><name sortKey="Willemze, A" uniqKey="Willemze A">A Willemze</name></author><author><name sortKey="Ioan Facsinay, A" uniqKey="Ioan Facsinay A">A Ioan-Facsinay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mikuls, Tr" uniqKey="Mikuls T">TR Mikuls</name></author><author><name sortKey="Payne, Jb" uniqKey="Payne J">JB Payne</name></author><author><name sortKey="Reinhardt, Ra" uniqKey="Reinhardt R">RA Reinhardt</name></author><author><name sortKey="Thiele, Gm" uniqKey="Thiele G">GM Thiele</name></author><author><name sortKey="Maziarz, E" uniqKey="Maziarz E">E Maziarz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mikuls, Tr" uniqKey="Mikuls T">TR Mikuls</name></author><author><name sortKey="Thiele, Gm" uniqKey="Thiele G">GM Thiele</name></author><author><name sortKey="Deane, Kd" uniqKey="Deane K">KD Deane</name></author><author><name sortKey="Payne, Jb" uniqKey="Payne J">JB Payne</name></author><author><name sortKey="O Ell, Jr" uniqKey="O Ell J">JR O’Dell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blaschke, S" uniqKey="Blaschke S">S Blaschke</name></author><author><name sortKey="Schwarz, G" uniqKey="Schwarz G">G Schwarz</name></author><author><name sortKey="Moneke, D" uniqKey="Moneke D">D Moneke</name></author><author><name sortKey="Binder, L" uniqKey="Binder L">L Binder</name></author><author><name sortKey="Muller, G" uniqKey="Muller G">G Müller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tzang, Bs" uniqKey="Tzang B">BS Tzang</name></author><author><name sortKey="Tsai, Cc" uniqKey="Tsai C">CC Tsai</name></author><author><name sortKey="Tsay, Gj" uniqKey="Tsay G">GJ Tsay</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name></author><author><name sortKey="Sun, Ys" uniqKey="Sun Y">YS Sun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Da Rocha Sobrinho, Hm" uniqKey="Da Rocha Sobrinho H">HM da Rocha Sobrinho</name></author><author><name sortKey="Jarach, R" uniqKey="Jarach R">R Jarach</name></author><author><name sortKey="Da Silva, Na" uniqKey="Da Silva N">NA da Silva</name></author><author><name sortKey="Shio, Mt" uniqKey="Shio M">MT Shio</name></author><author><name sortKey="Jancar, S" uniqKey="Jancar S">S Jancar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sawitzke, A" uniqKey="Sawitzke A">A Sawitzke</name></author><author><name sortKey="Joyner, D" uniqKey="Joyner D">D Joyner</name></author><author><name sortKey="Knudtson, K" uniqKey="Knudtson K">K Knudtson</name></author><author><name sortKey="Mu, Hh" uniqKey="Mu H">HH Mu</name></author><author><name sortKey="Cole, B" uniqKey="Cole B">B Cole</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scotet, E" uniqKey="Scotet E">E Scotet</name></author><author><name sortKey="David Ameline, J" uniqKey="David Ameline J">J David-Ameline</name></author><author><name sortKey="Peyrat, Ma" uniqKey="Peyrat M">MA Peyrat</name></author><author><name sortKey="Moreau Aubry, A" uniqKey="Moreau Aubry A">A Moreau-Aubry</name></author><author><name sortKey="Pinczon, D" uniqKey="Pinczon D">D Pinczon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lunemann, Jd" uniqKey="Lunemann J">JD Lunemann</name></author><author><name sortKey="Frey, O" uniqKey="Frey O">O Frey</name></author><author><name sortKey="Eidner, T" uniqKey="Eidner T">T Eidner</name></author><author><name sortKey="Baier, M" uniqKey="Baier M">M Baier</name></author><author><name sortKey="Roberts, S" uniqKey="Roberts S">S Roberts</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klatt, T" uniqKey="Klatt T">T Klatt</name></author><author><name sortKey="Ouyang, Q" uniqKey="Ouyang Q">Q Ouyang</name></author><author><name sortKey="Flad, T" uniqKey="Flad T">T Flad</name></author><author><name sortKey="Koetter, I" uniqKey="Koetter I">I Koetter</name></author><author><name sortKey="Buhring, Hj" uniqKey="Buhring H">HJ Bühring</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ford, Dk" uniqKey="Ford D">DK Ford</name></author><author><name sortKey="Da Roza, Dm" uniqKey="Da Roza D">DM da Roza</name></author><author><name sortKey="Schulzer, M" uniqKey="Schulzer M">M Schulzer</name></author><author><name sortKey="Reid, Gd" uniqKey="Reid G">GD Reid</name></author><author><name sortKey="Denegri, Jf" uniqKey="Denegri J">JF Denegri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Doran, Mf" uniqKey="Doran M">MF Doran</name></author><author><name sortKey="Gabriel, Se" uniqKey="Gabriel S">SE Gabriel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cole, Bc" uniqKey="Cole B">BC Cole</name></author><author><name sortKey="Golightly Rowland, L" uniqKey="Golightly Rowland L">L Golightly-Rowland</name></author><author><name sortKey="Ward, Jr" uniqKey="Ward J">JR Ward</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bartold, Pm" uniqKey="Bartold P">PM Bartold</name></author><author><name sortKey="Marino, V" uniqKey="Marino V">V Marino</name></author><author><name sortKey="Cantley, M" uniqKey="Cantley M">M Cantley</name></author><author><name sortKey="Haynes, Dr" uniqKey="Haynes D">DR Haynes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kinloch, Aj" uniqKey="Kinloch A">AJ Kinloch</name></author><author><name sortKey="Alzabin, S" uniqKey="Alzabin S">S Alzabin</name></author><author><name sortKey="Brintnell, W" uniqKey="Brintnell W">W Brintnell</name></author><author><name sortKey="Wilson, E" uniqKey="Wilson E">E Wilson</name></author><author><name sortKey="Barra, L" uniqKey="Barra L">L Barra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cantley, Md" uniqKey="Cantley M">MD Cantley</name></author><author><name sortKey="Haynes, Dr" uniqKey="Haynes D">DR Haynes</name></author><author><name sortKey="Marino, V" uniqKey="Marino V">V Marino</name></author><author><name sortKey="Bartold, Pm" uniqKey="Bartold P">PM Bartold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cole, Bc" uniqKey="Cole B">BC Cole</name></author><author><name sortKey="Griffiths, Mm" uniqKey="Griffiths M">MM Griffiths</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maresz, Kj" uniqKey="Maresz K">KJ Maresz</name></author><author><name sortKey="Hellvard, A" uniqKey="Hellvard A">A Hellvard</name></author><author><name sortKey="Sroka, A" uniqKey="Sroka A">A Sroka</name></author><author><name sortKey="Adamowicz, K" uniqKey="Adamowicz K">K Adamowicz</name></author><author><name sortKey="Bielecka, E" uniqKey="Bielecka E">E Bielecka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, Hj" uniqKey="Wu H">HJ Wu</name></author><author><name sortKey="Ivanov, Ii" uniqKey="Ivanov I">II Ivanov</name></author><author><name sortKey="Darce, J" uniqKey="Darce J">J Darce</name></author><author><name sortKey="Hattori, K" uniqKey="Hattori K">K Hattori</name></author><author><name sortKey="Shima, T" uniqKey="Shima T">T Shima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simelyte, E" uniqKey="Simelyte E">E Simelyte</name></author><author><name sortKey="Rimpil Inen, M" uniqKey="Rimpil Inen M">M Rimpiläinen</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X Zhang</name></author><author><name sortKey="Toivanen, P" uniqKey="Toivanen P">P Toivanen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Caccese, Rg" uniqKey="Caccese R">RG Caccese</name></author><author><name sortKey="Zimmerman, Jl" uniqKey="Zimmerman J">JL Zimmerman</name></author><author><name sortKey="Carlson, Rp" uniqKey="Carlson R">RP Carlson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuwana, Y" uniqKey="Kuwana Y">Y Kuwana</name></author><author><name sortKey="Takei, M" uniqKey="Takei M">M Takei</name></author><author><name sortKey="Yajima, M" uniqKey="Yajima M">M Yajima</name></author><author><name sortKey="Imadome, K" uniqKey="Imadome K">K Imadome</name></author><author><name sortKey="Inomata, H" uniqKey="Inomata H">H Inomata</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Warde, N" uniqKey="Warde N">N Warde</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iwakura, Y" uniqKey="Iwakura Y">Y Iwakura</name></author><author><name sortKey="Tosu, M" uniqKey="Tosu M">M Tosu</name></author><author><name sortKey="Yoshida, E" uniqKey="Yoshida E">E Yoshida</name></author><author><name sortKey="Takiguchi, M" uniqKey="Takiguchi M">M Takiguchi</name></author><author><name sortKey="Sato, K" uniqKey="Sato K">K Sato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aletaha, D" uniqKey="Aletaha D">D Aletaha</name></author><author><name sortKey="Neogi, T" uniqKey="Neogi T">T Neogi</name></author><author><name sortKey="Silman, Aj" uniqKey="Silman A">AJ Silman</name></author><author><name sortKey="Funovits, J" uniqKey="Funovits J">J Funovits</name></author><author><name sortKey="Felson, Dt" uniqKey="Felson D">DT Felson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aletaha, D" uniqKey="Aletaha D">D Aletaha</name></author><author><name sortKey="Neogi, T" uniqKey="Neogi T">T Neogi</name></author><author><name sortKey="Silman, Aj" uniqKey="Silman A">AJ Silman</name></author><author><name sortKey="Funovits, J" uniqKey="Funovits J">J Funovits</name></author><author><name sortKey="Felson, Dt" uniqKey="Felson D">DT Felson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van De Stadt, La" uniqKey="Van De Stadt L">LA van de Stadt</name></author><author><name sortKey="De Koning, Mh" uniqKey="De Koning M">MH de Koning</name></author><author><name sortKey="Van De Stadt, Rj" uniqKey="Van De Stadt R">RJ van de Stadt</name></author><author><name sortKey="Wolbink, G" uniqKey="Wolbink G">G Wolbink</name></author><author><name sortKey="Dijkmans, Ba" uniqKey="Dijkmans B">BA Dijkmans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wegner, N" uniqKey="Wegner N">N Wegner</name></author><author><name sortKey="Lundberg, K" uniqKey="Lundberg K">K Lundberg</name></author><author><name sortKey="Kinloch, A" uniqKey="Kinloch A">A Kinloch</name></author><author><name sortKey="Fisher, B" uniqKey="Fisher B">B Fisher</name></author><author><name sortKey="Malmstrom, V" uniqKey="Malmstrom V">V Malmström</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wegner, N" uniqKey="Wegner N">N Wegner</name></author><author><name sortKey="Wait, R" uniqKey="Wait R">R Wait</name></author><author><name sortKey="Sroka, A" uniqKey="Sroka A">A Sroka</name></author><author><name sortKey="Eick, S" uniqKey="Eick S">S Eick</name></author><author><name sortKey="Nguyen, Ka" uniqKey="Nguyen K">KA Nguyen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vossenaar, Er" uniqKey="Vossenaar E">ER Vossenaar</name></author><author><name sortKey="Radstake, Tr" uniqKey="Radstake T">TR Radstake</name></author><author><name sortKey="Van Der Heijden, A" uniqKey="Van Der Heijden A">A van der Heijden</name></author><author><name sortKey="Van Mansum, Ma" uniqKey="Van Mansum M">MA van Mansum</name></author><author><name sortKey="Dieteren, C" uniqKey="Dieteren C">C Dieteren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Foulquier, C" uniqKey="Foulquier C">C Foulquier</name></author><author><name sortKey="Sebbag, M" uniqKey="Sebbag M">M Sebbag</name></author><author><name sortKey="Clavel, C" uniqKey="Clavel C">C Clavel</name></author><author><name sortKey="Chapuy Regaud, S" uniqKey="Chapuy Regaud S">S Chapuy-Regaud</name></author><author><name sortKey="Al Badine, R" uniqKey="Al Badine R">R Al Badine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mangat, P" uniqKey="Mangat P">P Mangat</name></author><author><name sortKey="Wegner, N" uniqKey="Wegner N">N Wegner</name></author><author><name sortKey="Venables, Pj" uniqKey="Venables P">PJ Venables</name></author><author><name sortKey="Potempa, J" uniqKey="Potempa J">J Potempa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, Y" uniqKey="Yu Y">Y Yu</name></author><author><name sortKey="Su, K" uniqKey="Su K">K Su</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khandpur, R" uniqKey="Khandpur R">R Khandpur</name></author><author><name sortKey="Carmona Rivera, C" uniqKey="Carmona Rivera C">C Carmona-Rivera</name></author><author><name sortKey="Vivekanandan Giri, A" uniqKey="Vivekanandan Giri A">A Vivekanandan-Giri</name></author><author><name sortKey="Gizinski, A" uniqKey="Gizinski A">A Gizinski</name></author><author><name sortKey="Yalavarthi, S" uniqKey="Yalavarthi S">S Yalavarthi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lundberg, K" uniqKey="Lundberg K">K Lundberg</name></author><author><name sortKey="Nijenhuis, S" uniqKey="Nijenhuis S">S Nijenhuis</name></author><author><name sortKey="Vossenaar, Er" uniqKey="Vossenaar E">ER Vossenaar</name></author><author><name sortKey="Palmblad, K" uniqKey="Palmblad K">K Palmblad</name></author><author><name sortKey="Van Venrooij, Wj" uniqKey="Van Venrooij W">WJ van Venrooij</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lundberg, K" uniqKey="Lundberg K">K Lundberg</name></author><author><name sortKey="Kinloch, A" uniqKey="Kinloch A">A Kinloch</name></author><author><name sortKey="Fisher, Ba" uniqKey="Fisher B">BA Fisher</name></author><author><name sortKey="Wegner, N" uniqKey="Wegner N">N Wegner</name></author><author><name sortKey="Wait, R" uniqKey="Wait R">R Wait</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Birkenfeld, P" uniqKey="Birkenfeld P">P Birkenfeld</name></author><author><name sortKey="Haratz, N" uniqKey="Haratz N">N Haratz</name></author><author><name sortKey="Klein, G" uniqKey="Klein G">G Klein</name></author><author><name sortKey="Sulitzeanu, D" uniqKey="Sulitzeanu D">D Sulitzeanu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Albani, S" uniqKey="Albani S">S Albani</name></author><author><name sortKey="Keystone, Ec" uniqKey="Keystone E">EC Keystone</name></author><author><name sortKey="Nelson, Jl" uniqKey="Nelson J">JL Nelson</name></author><author><name sortKey="Ollier, We" uniqKey="Ollier W">WE Ollier</name></author><author><name sortKey="La Cava, A" uniqKey="La Cava A">A La Cava</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wilson, C" uniqKey="Wilson C">C Wilson</name></author><author><name sortKey="Tiwana, H" uniqKey="Tiwana H">H Tiwana</name></author><author><name sortKey="Ebringer, A" uniqKey="Ebringer A">A Ebringer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kogure, A" uniqKey="Kogure A">A Kogure</name></author><author><name sortKey="Miyata, M" uniqKey="Miyata M">M Miyata</name></author><author><name sortKey="Nishimaki, T" uniqKey="Nishimaki T">T Nishimaki</name></author><author><name sortKey="Kasukawa, R" uniqKey="Kasukawa R">R Kasukawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Celis, L" uniqKey="Celis L">L Celis</name></author><author><name sortKey="Vandevyver, C" uniqKey="Vandevyver C">C Vandevyver</name></author><author><name sortKey="Geusens, P" uniqKey="Geusens P">P Geusens</name></author><author><name sortKey="Dequeker, J" uniqKey="Dequeker J">J Dequeker</name></author><author><name sortKey="Raus, J" uniqKey="Raus J">J Raus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sfriso, P" uniqKey="Sfriso P">P Sfriso</name></author><author><name sortKey="Ghirardello, A" uniqKey="Ghirardello A">A Ghirardello</name></author><author><name sortKey="Botsios, C" uniqKey="Botsios C">C Botsios</name></author><author><name sortKey="Tonon, M" uniqKey="Tonon M">M Tonon</name></author><author><name sortKey="Zen, M" uniqKey="Zen M">M Zen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barksby, He" uniqKey="Barksby H">HE Barksby</name></author><author><name sortKey="Nile, Cj" uniqKey="Nile C">CJ Nile</name></author><author><name sortKey="Jaedicke, Km" uniqKey="Jaedicke K">KM Jaedicke</name></author><author><name sortKey="Taylor, Jj" uniqKey="Taylor J">JJ Taylor</name></author><author><name sortKey="Preshaw, Pm" uniqKey="Preshaw P">PM Preshaw</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nile, Cj" uniqKey="Nile C">CJ Nile</name></author><author><name sortKey="Barksby, E" uniqKey="Barksby E">E Barksby</name></author><author><name sortKey="Jitprasertwong, P" uniqKey="Jitprasertwong P">P Jitprasertwong</name></author><author><name sortKey="Preshaw, Pm" uniqKey="Preshaw P">PM Preshaw</name></author><author><name sortKey="Taylor, Jj" uniqKey="Taylor J">JJ Taylor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dziarski, R" uniqKey="Dziarski R">R Dziarski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Je" uniqKey="Wang J">JE Wang</name></author><author><name sortKey="J Rgensen, Pf" uniqKey="J Rgensen P">PF Jørgensen</name></author><author><name sortKey="Ellingsen, Ea" uniqKey="Ellingsen E">EA Ellingsen</name></author><author><name sortKey="Almiof, M" uniqKey="Almiof M">M Almiöf</name></author><author><name sortKey="Thiemermann, C" uniqKey="Thiemermann C">C Thiemermann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paliard, X" uniqKey="Paliard X">X Paliard</name></author><author><name sortKey="West, Sg" uniqKey="West S">SG West</name></author><author><name sortKey="Lafferty, Ja" uniqKey="Lafferty J">JA Lafferty</name></author><author><name sortKey="Clements, Jr" uniqKey="Clements J">JR Clements</name></author><author><name sortKey="Kappler, Jw" uniqKey="Kappler J">JW Kappler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Howell, Md" uniqKey="Howell M">MD Howell</name></author><author><name sortKey="Diveley, Jp" uniqKey="Diveley J">JP Diveley</name></author><author><name sortKey="Lundeen, Ka" uniqKey="Lundeen K">KA Lundeen</name></author><author><name sortKey="Esty, A" uniqKey="Esty A">A Esty</name></author><author><name sortKey="Winters, St" uniqKey="Winters S">ST Winters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rickinson, Ab" uniqKey="Rickinson A">AB Rickinson</name></author><author><name sortKey="Moss, Dj" uniqKey="Moss D">DJ Moss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hsiao, Fc" uniqKey="Hsiao F">FC Hsiao</name></author><author><name sortKey="Lin, M" uniqKey="Lin M">M Lin</name></author><author><name sortKey="Tai, A" uniqKey="Tai A">A Tai</name></author><author><name sortKey="Chen, G" uniqKey="Chen G">G Chen</name></author><author><name sortKey="Huber, Bt" uniqKey="Huber B">BT Huber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schwab, Jh" uniqKey="Schwab J">JH Schwab</name></author><author><name sortKey="Brown, Rr" uniqKey="Brown R">RR Brown</name></author><author><name sortKey="Anderle, Sk" uniqKey="Anderle S">SK Anderle</name></author><author><name sortKey="Schlievert, Pm" uniqKey="Schlievert P">PM Schlievert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okahashi, N" uniqKey="Okahashi N">N Okahashi</name></author><author><name sortKey="Sakurai, A" uniqKey="Sakurai A">A Sakurai</name></author><author><name sortKey="Nakagawa, I" uniqKey="Nakagawa I">I Nakagawa</name></author><author><name sortKey="Fujiwara, T" uniqKey="Fujiwara T">T Fujiwara</name></author><author><name sortKey="Kawabata, S" uniqKey="Kawabata S">S Kawabata</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kotake, S" uniqKey="Kotake S">S Kotake</name></author><author><name sortKey="Udagawa, N" uniqKey="Udagawa N">N Udagawa</name></author><author><name sortKey="Hakoda, M" uniqKey="Hakoda M">M Hakoda</name></author><author><name sortKey="Mogi, M" uniqKey="Mogi M">M Mogi</name></author><author><name sortKey="Yano, K" uniqKey="Yano K">K Yano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, X" uniqKey="Zhang X">X Zhang</name></author><author><name sortKey="Aubin, Je" uniqKey="Aubin J">JE Aubin</name></author><author><name sortKey="Kim, Th" uniqKey="Kim T">TH Kim</name></author><author><name sortKey="Payne, U" uniqKey="Payne U">U Payne</name></author><author><name sortKey="Chiu, B" uniqKey="Chiu B">B Chiu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rohner, E" uniqKey="Rohner E">E Röhner</name></author><author><name sortKey="Detert, J" uniqKey="Detert J">J Detert</name></author><author><name sortKey="Kolar, P" uniqKey="Kolar P">P Kolar</name></author><author><name sortKey="Hocke, A" uniqKey="Hocke A">A Hocke</name></author><author><name sortKey="N Uessan, P" uniqKey="N Uessan P">P N’Guessan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roudier, J" uniqKey="Roudier J">J Roudier</name></author><author><name sortKey="Petersen, J" uniqKey="Petersen J">J Petersen</name></author><author><name sortKey="Rhodes, Gh" uniqKey="Rhodes G">GH Rhodes</name></author><author><name sortKey="Luka, J" uniqKey="Luka J">J Luka</name></author><author><name sortKey="Carson, Da" uniqKey="Carson D">DA Carson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101563152</journal-id><journal-id journal-id-type="pubmed-jr-id">39420</journal-id><journal-id journal-id-type="nlm-ta">J Clin Cell Immunol</journal-id><journal-id journal-id-type="iso-abbrev">J Clin Cell Immunol</journal-id><journal-title-group><journal-title>Journal of clinical & cellular immunology</journal-title></journal-title-group><issn pub-type="epub">2155-9899</issn></journal-meta><article-meta><article-id pub-id-type="pmid">25133066</article-id><article-id pub-id-type="pmc">4131749</article-id><article-id pub-id-type="doi">10.4172/2155-9899.1000174</article-id><article-id pub-id-type="manuscript">NIHMS558819</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Microbial Infection and Rheumatoid Arthritis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Li</surname><given-names>Song</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yu</surname><given-names>Yangsheng</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yue</surname><given-names>Yinshi</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Zhixin</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Su</surname><given-names>Kaihong</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref rid="FN1" ref-type="author-notes">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA</aff><aff id="A2"><label>2</label>The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA</aff><aff id="A3"><label>3</label>Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA</aff><author-notes><corresp id="FN1"><label>*</label>Corresponding author: Kaihong Su, Ph.D., Associate Professor, Department of Pathology and Microbiology, University of Nebraska Medical Center, LTC 11724, 987660 Nebraska Medical Center, Omaha, NE 68198-7660, USA, Tel: 402-559-7612; Fax: 402-559-7716; <email>ksu@unmc.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>11</day><month>3</month><year>2014</year></pub-date><pub-date pub-type="epub"><month>12</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>13</day><month>8</month><year>2014</year></pub-date><volume>4</volume><issue>6</issue><elocation-id>174</elocation-id><permissions><copyright-statement>Copyright: © 2013 Li S, et al.</copyright-statement><copyright-year>2013</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri xlink:href="http://omicsonline.org/microbial-infection-and-rheumatoid-arthritis-2155-9899.1000174.php?aid=21312"></self-uri><abstract><p id="P1">Rheumatoid arthritis (RA) is a complex autoimmune disease affecting 1–2% of general worldwide population. The etiopathogenesis of RA involves the interplay of multiple genetic risk factors and environmental triggers. Microbial infections are believed to play an important role in the initiation and perpetuation of RA. Recent clinical studies have shown the association of microbial infections with RA. Accumulated studies using animal models have also found that microbial infections can induce and/or exaggerate the symptoms of experimental arthritis. In this review, we have identified the most common microbial infections associated with RA in the literature and summarized the current evidence supporting their pathogenic role in RA. We also discussed the potential mechanisms whereby infection may promote the development of RA, such as generation of neo-autoantigens, induction of loss of tolerance by molecular mimicry, and bystander activation of the immune system.</p></abstract><kwd-group><kwd>Rheumatoid arthritis</kwd><kwd>Infection</kwd><kwd>Microbes</kwd><kwd>Etiopathogenesis</kwd></kwd-group></article-meta></front><body><sec sec-type="intro" id="S1"><title>Introduction</title><p id="P2">Rheumatoid arthritis (RA) is one of the most common inflammatory autoimmune diseases. It is characterized by persistent synovitis, systemic inflammation and production of autoantibodies [<xref rid="R1" ref-type="bibr">1</xref>]. The molecular mechanisms of RA pathogenesis are not fully understood. It is believed that approximately half of the risk factors for RA are attributed to genetic factors such as the human leukocyte antigen (HLA) alleles while the other half of the risks are environmental factors including infection and smoking [<xref rid="R2" ref-type="bibr">2</xref>]. Clinical and animal model studies have suggested that infections by many microorganisms, such as <italic>Porphyromonas gingivalis</italic> (<italic>P. gingivalis</italic>), <italic>Proteus mirabilis</italic> (<italic>P. mirabilis</italic>), Epstein–Barr virus (EBV), and mycoplasma contribute to the etiopathogenesis of RA (<xref rid="T1" ref-type="table">Table 1</xref>).</p><p id="P3">For this review, we first identified the most common microbial infections associated to RA in the literature [<xref rid="R3" ref-type="bibr">3</xref>–<xref rid="R5" ref-type="bibr">5</xref>] and then performed a key word search using “arthritis” and “name of the microorganism” for original publications in English in the databases including Pubmed/Medline, Embase, EBSCO, SCOPUS, and Cochrane Library till November, 2013. The candidate microorganisms included in our search were <italic>P. gingivalis, P. mirabilis</italic>, EBV, cytomegalovirus (CMV), human immunodeficiency virus (HIV), parvovirus, hepatitis virus, herpes virus, human T-lymphotropic virus 1 (HTLV-1), mycoplasma, <italic>Streptococcus pyogenes</italic> (<italic>S. pyogenes</italic>), Salmonella, mycobacterium, and enterobacterium. Thus, this review will discuss studies regarding to those microorganisms with RA and emphasize on <italic>P. gingivalis</italic> which shows the strongest association with RA. Our discussion is organized in three sections, namely, clinical association of infection with RA, induction of arthritis by infection in animal models, and the pathogenic mechanisms of infection in RA.</p></sec><sec id="S2"><title>Clinical Association of Infection with RA</title><sec id="S3"><title>Clinical co-existence of infection and RA</title><p id="P4">Periodontal disease (PD) is the most commonly associated RA disease. The association between the two has been considered since the early 1820s. PD is caused by chronic infection of approximately twenty different bacterial species, of which <italic>P. gingivalis, Prevotella intermedia, Tannerella forsythia,</italic> and <italic>Aggregatibacter actinomycetemcomitans</italic> are the most common ones. PD can progress from gingivitis to periodontitis and cause bone degeneration in the jaw. Clinical association studies consistently show that the prevalence of periodontitis is increased about two-fold in RA patients than non-RA patients. In a large study involving 4461 participants aged 60 or older in the US population, subjects with RA were more likely to have periodontitis (odds ratio (OR)=1.82) or complete tooth loss (edentulism, OR=2.27), compared to non-RA subjects after adjusting for age, gender, race/ethnicity, and smoking [<xref rid="R6" ref-type="bibr">6</xref>]. Another study reported that moderate to severe periodontitis was more prevalent in RA patients (51%) than age and gender matched osteoarthritis patients (26%) [<xref rid="R7" ref-type="bibr">7</xref>]. A recent study in the Dutch population confirmed the higher prevalence of severe periodontitis in RA patients [<xref rid="R8" ref-type="bibr">8</xref>]. They also reported that RA patients with severe periodontitis had higher DAS28 scores than RA patients with no or moderate periodontitis, suggesting that the severity of periodontitis is related to the severity of RA [<xref rid="R8" ref-type="bibr">8</xref>].</p><p id="P5">However, it is less clear that whether subjects with PD have increased incidence of RA. In a large prospective study involving 81,132 American women in the Nurses’ Health Study cohort, there is no increased risk of later-onset RA in subjects with a history of periodontal surgery and/ or tooth loss compared to subjects with healthy periodontal conditions [<xref rid="R9" ref-type="bibr">9</xref>]. In another large prospective study using the National Health and Nutrition Examination Survey cohort, subjects with PD experienced higher odds of prevalent/incident RA, but most odd ratios were not statistically significant [<xref rid="R10" ref-type="bibr">10</xref>]. It is also important to keep in mind that both studies are not specifically designed to examine the relationship between PD and RA. It is quite possible that there are missing data about PD and RA status in these cohorts and differential RA and PD ascertainment bias may also complicate the interpretation of data. Taken together, clinical studies have clearly shown the association of periodontal infection with RA. However, more longitudinal studies using well-defined populations are necessary to support the conclusion that periodontal infection is a risk factor for the development of RA.</p><p id="P6">Another common infection associated with RA is <italic>Proteus</italic>-caused urine tract infection. Patients with RA had significantly increased incidence of urinary tract infection and subclinical/asymptomatic bacteriuria compared to non-RA subjects [<xref rid="R11" ref-type="bibr">11</xref>]. <italic>P. mirabilis</italic> bacteria were isolated at a higher rate from urine samples of both female (63%) and male (50%) patients with RA than from healthy female (32–35%) and male (7–11%) subjects and patients with other autoimmune diseases including osteoarthritis, fibromyalgia, and psoriasis [<xref rid="R12" ref-type="bibr">12</xref>]. These studies implicate a plausible role of <italic>Proteus</italic> microorganisms in the development of RA.</p><p id="P7">Furthermore, it has been well documented that infections by a range of bacteria and viruses frequently manifest rheumatic diseases, including reactive arthritis. Gastrointestinal or genitourinary infections with <italic>Salmonella, Shigella, Campylobacter, Yersinia</italic>, and <italic>Chlamydia trachomatis</italic> may cause inflammatory oligoarticular or polyarticular sterile arthritis, usually starting within four weeks of infection [<xref rid="R13" ref-type="bibr">13</xref>]. Viruses including HIV, parvovirus, hepatitis viruses B and C, alpha-viruses like Chikungunya can cause acute or chronic forms of arthritis, and in some cases, mimic RA [<xref rid="R13" ref-type="bibr">13</xref>]. The precedence of infection over clinical arthritis suggests a causal relationship of the two events.</p><p id="P8">In summary, the clinical association studies suggest that infection is a risk factor for the development of RA. In addition, antibiotics such as sulphasalazine, minocycline, and rifampicin have been reported to be beneficial for the treatment of RA [<xref rid="R14" ref-type="bibr">14</xref>,<xref rid="R15" ref-type="bibr">15</xref>]. Reversely, periodontal treatments (oral hygiene and supragingival scaling) decreased the DAS28-CRP scores in RA patients [<xref rid="R16" ref-type="bibr">16</xref>], further implicating the pathogenic role of microbial infection in RA.</p></sec><sec id="S4"><title>Presence of microbial contents in RA tissues</title><p id="P9">Besides the disease association, the presence of microbial contents in RA tissues provides additional evidence for the correlation between infection and RA. Molecular techniques such as PCR and DNA/RNA-<italic>in situ</italic> hybridization have been widely used to detect bacterial or viral infections. <italic>P. gingivalis</italic> [<xref rid="R17" ref-type="bibr">17</xref>], mycoplasma [<xref rid="R18" ref-type="bibr">18</xref>,<xref rid="R19" ref-type="bibr">19</xref>], parvovirus [<xref rid="R20" ref-type="bibr">20</xref>], EBV [<xref rid="R21" ref-type="bibr">21</xref>,<xref rid="R22" ref-type="bibr">22</xref>], and cytomegalovirus (CMV) [<xref rid="R22" ref-type="bibr">22</xref>,<xref rid="R23" ref-type="bibr">23</xref>] have been identified in the synovial fluid, synovial membranes or serum samples from RA patients. Herpes viruses were detected in salivary cells and circulating lymphocytes from RA patients [<xref rid="R24" ref-type="bibr">24</xref>,<xref rid="R25" ref-type="bibr">25</xref>]. Besides nucleic acids, other microbial components can be used in the detection of infections in RA patients. Bacterial fatty acids, peptidoglycan, and muramic acid quantified by techniques such as gas-liquid chromatography (GLC), enzyme-linked immunosorbent assays (ELISA) and mass spectrometry have been used to detect the presence of microbes in RA samples [<xref rid="R26" ref-type="bibr">26</xref>–<xref rid="R29" ref-type="bibr">29</xref>]. For example, in a cohort of patients with early RA before any specific treatment, analyses of bacterial cellular fatty acids by GLC revealed the abundance of anaerobic bacteria in the intestinal flora of RA patients, implicating a possible role of intestinal anaerobic bacteria in the development of RA [<xref rid="R26" ref-type="bibr">26</xref>–<xref rid="R29" ref-type="bibr">29</xref>].</p></sec><sec id="S5" sec-type="subjects"><title>Immune response to microbes in RA patients</title><p id="P10">Another strategy to detect previous and ongoing infections is to measure the immune responses to microbial components in patients. Indeed, antibodies against infectious microbes were detected in the sera of early RA patients and the levels of these antibodies correlated with the disease activity of RA. For example, elevated levels of IgM and IgA antibodies to <italic>P. mirabilis</italic> were found in rheumatoid factor (RF)-positive early RA patients [<xref rid="R30" ref-type="bibr">30</xref>]. The levels of anti-<italic>P. mirabilis</italic> antibodies in RA patients went down after one year of treatment and this decrease was significantly correlated with the decrease in a modified Stoke disease activity index in RA patients [<xref rid="R31" ref-type="bibr">31</xref>]. The specific antigens from P. mirabilis were later identified as haemolysin and urease [<xref rid="R32" ref-type="bibr">32</xref>,<xref rid="R33" ref-type="bibr">33</xref>].</p><p id="P11">Another prominent example is that increased antibody responses to <italic>P. gingivalis</italic>, one of the common bacteria causing PD, were detected in RA patient sera and synovial fluid. Furthermore, the anti-<italic>P. gingivalis</italic> antibody levels were correlated with the titers of anti-cyclic citrullinated peptide (CCP) antibodies (the recently added RA diagnosis criteria) in RA patients [<xref rid="R34" ref-type="bibr">34</xref>,<xref rid="R35" ref-type="bibr">35</xref>]. Interestingly, a recent study showed that anti-<italic>P. gingivalis</italic> antibodies were significantly associated with the presence of RA-related autoantibodies (anti-CCP and rheumatoid factor) in individuals at high risk of RA [<xref rid="R36" ref-type="bibr">36</xref>]. This result supports the hypothesis that infection by <italic>P. gingivalis</italic> may play a central role in the early loss of self-tolerance that occurs in the pathogenesis of RA. Increased antibody responses to other infectious agents, such as EBV [<xref rid="R37" ref-type="bibr">37</xref>], B19 parvovirus [<xref rid="R38" ref-type="bibr">38</xref>], and mycoplasma [<xref rid="R39" ref-type="bibr">39</xref>,<xref rid="R40" ref-type="bibr">40</xref>], have also been reported in RA patients. Furthermore, T cell responses to EBV [<xref rid="R41" ref-type="bibr">41</xref>–<xref rid="R43" ref-type="bibr">43</xref>] and CMV [<xref rid="R44" ref-type="bibr">44</xref>] were detected in the inflamed joints from RA patients.</p><p id="P12">In summary, clinical studies using human materials revealed a possible causative link between microbial infection and RA. However, more definitive studies in well characterized cohorts are necessary before we can conclude that microbial infection plays a crucial role in the initiation and perpetuation of RA. Moreover, the “chicken or egg” relationship between infection and RA may be hard to address in human studies. First, the RA-susceptible genetic and environmental factors, such as predisposed genes and living habits, may cause increased risks to infection even before or in the early stage of RA. Second, the RA-associated abnormal immune response and immunosuppressive medicine may contribute to decreased host defense to infection [<xref rid="R45" ref-type="bibr">45</xref>]. In this case, studies using animal models are very useful as experimental animals normally have homogeneous genetic and environmental backgrounds.</p></sec></sec><sec id="S6"><title>Induction of Arthritis by Infections in Animal Models</title><p id="P13">Animal studies can directly address the causal relationship between infection and RA in accordant to Koch’s postulates, although there is no perfect animal model for human RA yet. Infections by <italic>P. gingivalis</italic> or mycoplasma induced or aggravated experimental arthritis in mice or rats [<xref rid="R46" ref-type="bibr">46</xref>–<xref rid="R50" ref-type="bibr">50</xref>]. Interestingly, a very recent study showed that <italic>P. gingivalis</italic> facilitated the development and progression of destructive arthritis in CIA mice through its unique bacterial peptidylarginine deiminase (PPAD) [<xref rid="R51" ref-type="bibr">51</xref>]. PPAD can lead to the generation of RA related citrullinated autoantigens by converting protein arginine residues to citrulline. This result suggests that <italic>P. gingivalis</italic> infection may play an important role in the loss of tolerance to citrullinated proteins in RA, implicating the causative link between infection and RA. In another study, experimental arthritis was strongly attenuated in the K/BxN mouse model under germ-free (GF) conditions, featured with reduced Th<sub>17</sub> cells. Furthermore, introduction of segmented filamentous bacteria into GF mice reinstated the production of autoantibodies and arthritis symptoms [<xref rid="R52" ref-type="bibr">52</xref>]. This study shows that a single commensal microbe can drive the autoimmune arthritis possibly via its ability to promote Th<sub>17</sub> cells.</p><p id="P14">Components derived from infectious pathogens can also induce or potentiate arthritis in animal models. For example, bacterial cell wall extracts can induce chronic arthritis in certain susceptible rat strains; and bacterial lipopolysaccharide (LPS) potentiates type II collagen-induced arthritis in mice [<xref rid="R53" ref-type="bibr">53</xref>,<xref rid="R54" ref-type="bibr">54</xref>]. Interestingly, EBV does not infect mice; and in a humanized mice model, EBV induced erosive arthritis with many features resembling those of RA [<xref rid="R55" ref-type="bibr">55</xref>,<xref rid="R56" ref-type="bibr">56</xref>]. Human T-lymphotropic virus 1 (HTLV-1) transgenic mice also developed inflammatory arthropathy, resembling RA [<xref rid="R57" ref-type="bibr">57</xref>].</p><p id="P15">In summary, the animal studies provide direct evidence for the causal relationship between infection and RA in experimental arthritis. Combined with the clinical association between infection and RA in human patients, it is convincing that microbial infection contributes to the etiopathogenesis of RA. However, the translation of findings from animals to humans is still arbitrary to some extent. First, adjuvant is used in the immunization protocol in these arthritis animal models. Adjuvant is known to strongly boost immune responses, and in the mean time, may also invoke immune responses to self-antigens. Second, the methods of delivering microbes in animal studies may differ from the routes of microbial evasion in humans. ird, arthritis symptoms in animals only resemble the joint inflammation in human RA, which may not represent the natural course of RA development in human patients. Nevertheless, these problems are common for animal of human diseases, and arthritis animal studies certainly provide valuable information for our understanding of RA pathogenesis.</p></sec><sec id="S7"><title>Pathogenic Mechanisms of Infection in RA</title><sec id="S8"><title>Generation of neo-autoantigens</title><p id="P16">Autoantibodies play a crucial role in the development of RA. In fact, serum RF and anti-citrullinated protein antibodies (ACPAs) are included in the <italic>2010 ACR/EULAR</italic> diagnostic criteria of RA [<xref rid="R58" ref-type="bibr">58</xref>,<xref rid="R59" ref-type="bibr">59</xref>]. ACPAs are highly specific for RA and appear years earlier than the clinical diagnosis of RA [<xref rid="R60" ref-type="bibr">60</xref>]. Protein citrullination is a post-translational modification catalyzed by the enzyme peptidylarginine deiminase (PAD). <italic>P. gingivalis</italic> is the only prokaryotic organism that contains PAD. Recent studies showed that <italic>P. gingivalis-</italic>mediated citrullination of bacterial and host proteins provided an important mechanism for generating neo-antigens that drive the ACPA responses in RA [<xref rid="R61" ref-type="bibr">61</xref>]. Endogenous citrullinated proteins such as citrullinated α-enolase were abundant in <italic>P. gingivalis</italic>; and <italic>P. gingivalis</italic> PAD can citrullinate human proteins including common RA antigens fibrinogen and α-enolase [<xref rid="R62" ref-type="bibr">62</xref>]. Interestingly, a recent animal study showed that <italic>P. gingivalis</italic> facilitated the development and progression of destructive arthritis through its bacterial PAD enzymatic activities [<xref rid="R51" ref-type="bibr">51</xref>]. Microbial infections may also facilitate the citrullination process by activating host monocytes and neutrophils which express high levels of PAD [<xref rid="R63" ref-type="bibr">63</xref>–<xref rid="R65" ref-type="bibr">65</xref>].</p><p id="P17">Neutrophil extracellular trap (NET) is a structure released by activated neutrophils. It is composed of decondensed chromatins and granular molecules which can enhance the killing of extracellular microbes. It has been shown that bacterial LPS and some inflammatory cytokines can strongly induce NET. NET provides a source of autoantigens for several autoimmune diseases, such as vasculitis, systemic lupus erythematosus, and RA [<xref rid="R66" ref-type="bibr">66</xref>,<xref rid="R67" ref-type="bibr">67</xref>]. NET contains citrullinated RA autoantigens including α-enolase and vimentin. Furthermore, netting neutrophils have been found in synovial tissues, rheumatoid nodules, and skin from RA patients [<xref rid="R67" ref-type="bibr">67</xref>], implicating a role of NET in the pathogenesis of RA.</p><p id="P18">Collectively, microbial infections directly or indirectly induce the generation of citrullinated neo-autoantigens which may trigger the aberrant immune responses in RA [<xref rid="R68" ref-type="bibr">68</xref>].</p></sec><sec id="S9"><title>Loss of tolerance by molecular mimicry</title><p id="P19">Molecular mimicry plays an important role in the loss of tolerance in autoimmunity. Microbes may have elements that are similar in amino acid sequences or structure to self-proteins thus trigger autoantibody production through epitope spreading. For example, the <italic>P. gingivalis</italic> enolase and human α-enolase share 82% homology at the 17-amino acid immunodominant regions. Therefore, antibodies against bacteria enolase can recognize the homologous human α-enolase and promote the production of anti-human α-enolase autoantibodies. Indeed, the levels of anti-citrullinated human α-enolase antibodies were tightly correlated with the levels of antibodies to bacterial α-enolase in RA patients [<xref rid="R69" ref-type="bibr">69</xref>]. In addition, the affinity-purified antibodies to the human α-enolase peptide displayed cross-reactivity with the <italic>P. gingivalis</italic> enolase peptide [<xref rid="R69" ref-type="bibr">69</xref>]. Other examples include antibodies against EBV peptide p107 cross-react with the denatured human collagen and keratin [<xref rid="R70" ref-type="bibr">70</xref>]. Molecular mimicry also promotes autoreactive T cell activation and proliferation. The mimicry peptides for T cell activation are generally shorter and more linear compared to those of B cells. <italic>E. coli</italic> heat shock protein DnaJ contains a QKRAA motif that is also present in the HLA-DRB1 shared epitopes. DnaJ strongly activated RA synovial T cells which had passed the positive selection in the thymus through weak binding with the corresponding HLA epitopes [<xref rid="R71" ref-type="bibr">71</xref>,<xref rid="R72" ref-type="bibr">72</xref>]. Mycobacterial 65 kD heat shock protein (HSP65) shares homology with human HSPs. Clonal expansion of mycobacterial HSP65-reactive T lymphocytes was found in the synovial fluids and blood samples of RA patients. In addition, mycobacterial HSP65 can induce the proliferative response of mononuclear cells derived from RA synovial fluids [<xref rid="R73" ref-type="bibr">73</xref>,<xref rid="R74" ref-type="bibr">74</xref>]. These studies support the hypothesis that microbial molecular mimicry plays an important role in priming autoimmunity in patients with RA.</p></sec><sec id="S10"><title>Bystander activation of the immune system</title><p id="P20">Bystander activation is a process by which microbial products non-specifically activate lymphocytes and immune effecter cells. It has been shown that bystander activation also plays a role in driving the autoimmunity and tissue injury in RA. The pathogen-associated molecular patterns (PAMPs) can bind to the pattern recognition receptors (PRRs) and lead to both innate and adaptive immune cell activation [<xref rid="R75" ref-type="bibr">75</xref>]. <italic>P. gingivalis</italic> and <italic>E. coli</italic> LPS induced monocyte activation and the production of RA-associated cytokines interleukin (IL)-1 and IL-33 through the TLR pathways [<xref rid="R76" ref-type="bibr">76</xref>,<xref rid="R77" ref-type="bibr">77</xref>]. Peptidoglycan, a bacterial cell wall component, is a potent arthritogen. It can activate lymphocytes and induce production of cytokines and polyclonal autoantibodies including RF <italic>in vivo</italic> using animal models and <italic>n vitro</italic> using cell culture systems [<xref rid="R78" ref-type="bibr">78</xref>,<xref rid="R79" ref-type="bibr">79</xref>].</p></sec><sec id="S11"><title>Microbial superantigens</title><p id="P21">Superantigens have long been suggested to play a role in pathogenesis of autoimmune diseases. The frequency of Vβ14<sup>+</sup> T cells in the synovial fluid of affected joints are significantly higher than that in the peripheral blood of RA patients, implicating that the etiology of RA may involve initial activation of Vβ14<sup>+</sup> T cells by a Vβ14<sup>+</sup>-specific superantigen [<xref rid="R80" ref-type="bibr">80</xref>]. The skewed accumulation of Vβ14<sup>+</sup> T cells in RA synovial joints was confirmed by another study [<xref rid="R81" ref-type="bibr">81</xref>]. EBV infection of human lymphocytes can cause <italic>in vitro</italic> expansion of non-specific B cells and CD8<sup>+</sup> T cells, leading to polyclonal antibody production and cytotoxic T cell activation [<xref rid="R43" ref-type="bibr">43</xref>,<xref rid="R82" ref-type="bibr">82</xref>,<xref rid="R83" ref-type="bibr">83</xref>]. In animal models, several superantigens, such as mycoplasma arthritidis mitogen and toxic shock syndrome toxin, were able to exacerbate arthritis [<xref rid="R50" ref-type="bibr">50</xref>,<xref rid="R84" ref-type="bibr">84</xref>].</p></sec><sec id="S12"><title>Direct effects on joint tissues</title><p id="P22">Microbial infection can have direct activating or damaging effects on the joint tissues. For example, <italic>Streptococcus pyogenes</italic> infection resulted in the increased expression of receptor activator of NF-κB ligand (RANKL) in mouse osteoblasts in cell culture [<xref rid="R85" ref-type="bibr">85</xref>,<xref rid="R86" ref-type="bibr">86</xref>]. In another study, Salmonella infection led to RANKL upregulation in synovial fibroblasts derived from mice [<xref rid="R87" ref-type="bibr">87</xref>]. Furthermore, co-cultures of Salmonella-infected synovial fibroblasts with osteoclast precursors resulted in the differentiation of multinucleated bone-resorbing, osteoclast-like cells and the formation of bone-resorbing pits [<xref rid="R87" ref-type="bibr">87</xref>]. This study provided evidence that Salmonella infection can mediate osteoclast differentiation and activation, which may contribute to bone destruction in infected joints. Recently, it was reported that <italic>P. gingivalis</italic> directly promotes early and later stages of apoptosis of human chondrocytes, which may contribute to the cartilage loss in RA patients [<xref rid="R88" ref-type="bibr">88</xref>].</p></sec></sec><sec sec-type="conclusions" id="S13"><title>Conclusion</title><p id="P23">RA is a complex autoimmune inflammatory disease. The etiopathogenesis of RA involves the interplay of multiple genetic risk factors and environmental triggers. Numerous studies have shown the clinical association of microbial infection with RA. Infection is often detected in early RA and can precede the occurrence of clinical arthritis. These observations suggest that infection contributes to the initiation and exaggeration of RA, arguing against the theory that the RA-associated infection is simply a sequela of immunosuppressive treatments. The pathogenic role of infection in RA is also suggested by studies using arthritis animal models. Among the RA associated microbes, <italic>P. gingivalis</italic> shows the greatest promise as a significant contributor to RA etiology. <italic>P. gingivalis</italic> is the only known prokaryotic organism that contains enzyme peptidylarginine deiminase (PAD) which is essential for the generation of citrullinated autoantigens. Human studies have shown the association of <italic>P. gingivalis</italic> infection with RA patients and individuals at high risk for RA. Animal studies also demonstrated that <italic>P. gingivalis</italic> infection facilitated the development and progression of destructive arthritis. And more interestingly, this effect is dependent on <italic>P. gingivalis</italic> PAD. Future prospective studies examining <italic>P. gingivalis</italic> infection in patients before and at the early-onset of RA using serial collections of patient sera are necessary to confirm the etiopathogenetic role of <italic>P. gingivalis</italic> in RA. Multivariate analyses stratified by RA related factors such as susceptible gene alleles and smoking are also required to pinpoint the role of <italic>P. gingivalis</italic> infection in RA. In addition, studies that elucidate the arthritogenic pathways of <italic>P. gingivalis</italic> infection hold great promise to provide therapeutic targets for the prevention and treatment of RA, a disease affecting 1–2% of the general world wide population.</p></sec></body><back><ack id="S14"><p>Research reported in this publication was supported in part by National Institutes of Health Grants AR059351 (to KS), AR048592, AI073174, AI074948, and AI076475 (to ZZ) and by a Research Support Fund grant from the Nebraska Medical Center and the University of Nebraska Medical Center (to KS).</p></ack><fn-group><fn id="FN2"><p>The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.</p></fn></fn-group><ref-list><ref id="R1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Scott</surname><given-names>DL</given-names></name><name><surname>Wolfe</surname><given-names>F</given-names></name><name><surname>Huizinga</surname><given-names>TW</given-names></name></person-group><year>2010</year><article-title>Rheumatoid arthritis</article-title><source>Lancet</source><volume>376</volume><fpage>1094</fpage><lpage>1108</lpage><pub-id pub-id-type="pmid">20870100</pub-id></element-citation></ref><ref id="R2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McInnes</surname><given-names>IB</given-names></name><name><surname>Schett</surname><given-names>G</given-names></name></person-group><year>2011</year><article-title>The pathogenesis of rheumatoid arthritis</article-title><source>N Engl J Med</source><volume>365</volume><fpage>2205</fpage><lpage>2219</lpage><pub-id pub-id-type="pmid">22150039</pub-id></element-citation></ref><ref id="R3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hitchon</surname><given-names>CA</given-names></name><name><surname>El-Gabalawy</surname><given-names>HS</given-names></name></person-group><year>2011</year><article-title>Infection and rheumatoid arthritis: still an open question</article-title><source>Curr Opin Rheumatol</source><volume>23</volume><fpage>352</fpage><lpage>357</lpage><pub-id pub-id-type="pmid">21532483</pub-id></element-citation></ref><ref id="R4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Carty</surname><given-names>SM</given-names></name><name><surname>Snowden</surname><given-names>N</given-names></name><name><surname>Silman</surname><given-names>AJ</given-names></name></person-group><year>2004</year><article-title>Should infection still be considered as the most likely triggering factor for rheumatoid arthritis?</article-title><source>Ann Rheum Dis</source><volume>63</volume><fpage>ii46</fpage><lpage>46ii49</lpage><pub-id pub-id-type="pmid">15479871</pub-id></element-citation></ref><ref id="R5"><label>5</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Silman</surname><given-names>AJ</given-names></name></person-group><person-group person-group-type="editor"><name><surname>Silman</surname><given-names>AJ</given-names></name><name><surname>Smolen</surname><given-names>JS</given-names></name><name><surname>Weinblatt</surname><given-names>ME</given-names></name><name><surname>Weisman</surname><given-names>MH</given-names></name></person-group><year>2009</year><article-title>Microbes in the pathogenesis of rheumatoid arthritis</article-title><source>Rheumatoid arthritis</source><edition>1</edition><publisher-name>Mosby Publishers</publisher-name><publisher-loc>USA</publisher-loc></element-citation></ref><ref id="R6"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Pablo</surname><given-names>P</given-names></name><name><surname>Dietrich</surname><given-names>T</given-names></name><name><surname>McAlindon</surname><given-names>TE</given-names></name></person-group><year>2008</year><article-title>Association of periodontal disease and tooth loss with rheumatoid arthritis in the US population</article-title><source>J Rheumatol</source><volume>35</volume><fpage>70</fpage><lpage>76</lpage><pub-id pub-id-type="pmid">18050377</pub-id></element-citation></ref><ref id="R7"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dissick</surname><given-names>A</given-names></name><name><surname>Redman</surname><given-names>RS</given-names></name><name><surname>Jones</surname><given-names>M</given-names></name><name><surname>Rangan</surname><given-names>BV</given-names></name><name><surname>Reimold</surname><given-names>A</given-names></name><etal></etal></person-group><year>2010</year><article-title>Association of periodontitis with rheumatoid arthritis: a pilot study</article-title><source>J Periodontol</source><volume>81</volume><fpage>223</fpage><lpage>230</lpage><pub-id pub-id-type="pmid">20151800</pub-id></element-citation></ref><ref id="R8"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Smit</surname><given-names>MD</given-names></name><name><surname>Westra</surname><given-names>J</given-names></name><name><surname>Vissink</surname><given-names>A</given-names></name><name><surname>Doornbos-van der Meer</surname><given-names>B</given-names></name><name><surname>Brouwer</surname><given-names>E</given-names></name><etal></etal></person-group><year>2012</year><article-title>Periodontitis in established rheumatoid arthritis patients: a cross-sectional clinical, microbiological and serological study</article-title><source>Arthritis Res Ther</source><volume>14</volume><fpage>R222</fpage><pub-id pub-id-type="pmid">23075462</pub-id></element-citation></ref><ref id="R9"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arkema</surname><given-names>EV</given-names></name><name><surname>Karlson</surname><given-names>EW</given-names></name><name><surname>Costenbader</surname><given-names>KH</given-names></name></person-group><year>2010</year><article-title>A prospective study of periodontal disease and risk of rheumatoid arthritis</article-title><source>J Rheumatol</source><volume>37</volume><fpage>1800</fpage><lpage>1804</lpage><pub-id pub-id-type="pmid">20595268</pub-id></element-citation></ref><ref id="R10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Demmer</surname><given-names>RT</given-names></name><name><surname>Molitor</surname><given-names>JA</given-names></name><name><surname>Jacobs</surname><given-names>DR</given-names><suffix>Jr</suffix></name><name><surname>Michalowicz</surname><given-names>BS</given-names></name></person-group><year>2011</year><article-title>Periodontal disease, tooth loss and incident rheumatoid arthritis: results from the First National Health and Nutrition Examination Survey and its epidemiological follow-up study</article-title><source>J Clin Periodontol</source><volume>38</volume><fpage>998</fpage><lpage>1006</lpage><pub-id pub-id-type="pmid">22092471</pub-id></element-citation></ref><ref id="R11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Puntis</surname><given-names>D</given-names></name><name><surname>Malik</surname><given-names>S</given-names></name><name><surname>Saravanan</surname><given-names>V</given-names></name><name><surname>Rynne</surname><given-names>M</given-names></name><name><surname>Heycock</surname><given-names>C</given-names></name><etal></etal></person-group><year>2013</year><article-title>Urinary tract infections in patients with rheumatoid arthritis</article-title><source>Clin Rheumatol</source><volume>32</volume><fpage>355</fpage><lpage>360</lpage><pub-id pub-id-type="pmid">23238605</pub-id></element-citation></ref><ref id="R12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Senior</surname><given-names>BW</given-names></name><name><surname>Anderson</surname><given-names>GA</given-names></name><name><surname>Morley</surname><given-names>KD</given-names></name><name><surname>Kerr</surname><given-names>MA</given-names></name></person-group><year>1999</year><article-title>Evidence that patients with rheumatoid arthritis have asymptomatic ‘non-significant’ Proteus mirabilis bacteriuria more frequently than healthy controls</article-title><source>J Infect</source><volume>38</volume><fpage>99</fpage><lpage>106</lpage><pub-id pub-id-type="pmid">10342649</pub-id></element-citation></ref><ref id="R13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Becker</surname><given-names>J</given-names></name><name><surname>Winthrop</surname><given-names>KL</given-names></name></person-group><year>2010</year><article-title>Update on rheumatic manifestations of infectious diseases</article-title><source>Curr Opin Rheumatol</source><volume>22</volume><fpage>72</fpage><lpage>77</lpage><pub-id pub-id-type="pmid">19910794</pub-id></element-citation></ref><ref id="R14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>O’Dell</surname><given-names>JR</given-names></name><name><surname>Blakely</surname><given-names>KW</given-names></name><name><surname>Mallek</surname><given-names>JA</given-names></name><name><surname>Eckhoff</surname><given-names>PJ</given-names></name><name><surname>Leff</surname><given-names>RD</given-names></name><etal></etal></person-group><year>2001</year><article-title>Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine</article-title><source>Arthritis Rheum</source><volume>44</volume><fpage>2235</fpage><lpage>2241</lpage><pub-id pub-id-type="pmid">11665963</pub-id></element-citation></ref><ref id="R15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pillemer</surname><given-names>S</given-names></name><name><surname>Gulko</surname><given-names>P</given-names></name><name><surname>Ligier</surname><given-names>S</given-names></name><name><surname>Yarboro</surname><given-names>C</given-names></name><name><surname>Gourley</surname><given-names>M</given-names></name><etal></etal></person-group><year>2003</year><article-title>Pilot clinical trial of intravenous doxycycline versus placebo for rheumatoid arthritis</article-title><source>J Rheumatol</source><volume>30</volume><fpage>41</fpage><lpage>43</lpage><pub-id pub-id-type="pmid">12508388</pub-id></element-citation></ref><ref id="R16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Okada</surname><given-names>M</given-names></name><name><surname>Kobayashi</surname><given-names>T</given-names></name><name><surname>Ito</surname><given-names>S</given-names></name><name><surname>Yokoyama</surname><given-names>T</given-names></name><name><surname>Abe</surname><given-names>A</given-names></name><etal></etal></person-group><year>2013</year><article-title>Periodontal Treatment Decreases Levels of Antibodies to Porphyromonas Gingivalis and Citrulline in Patients with Rheumatoid Arthritis and Periodontitis</article-title><source>J Periodontol</source></element-citation></ref><ref id="R17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Martinez-Martinez</surname><given-names>RE</given-names></name><name><surname>Abud-Mendoza</surname><given-names>C</given-names></name><name><surname>Patiño-Marin</surname><given-names>N</given-names></name><name><surname>Rizo-Rodríguez</surname><given-names>JC</given-names></name><name><surname>Little</surname><given-names>JW</given-names></name><etal></etal></person-group><year>2009</year><article-title>Detection of periodontal bacterial DNA in serum and synovial fluid in refractory rheumatoid arthritis patients</article-title><source>J Clin Periodontol</source><volume>36</volume><fpage>1004</fpage><lpage>1010</lpage><pub-id pub-id-type="pmid">19929953</pub-id></element-citation></ref><ref id="R18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schaeverbeke</surname><given-names>T</given-names></name><name><surname>Renaudin</surname><given-names>H</given-names></name><name><surname>Clerc</surname><given-names>M</given-names></name><name><surname>Lequen</surname><given-names>L</given-names></name><name><surname>Vernhes</surname><given-names>JP</given-names></name><etal></etal></person-group><year>1997</year><article-title>Systematic detection of mycoplasmas by culture and polymerase chain reaction (PCR) procedures in 209 synovial fluid samples</article-title><source>Br J Rheumatol</source><volume>36</volume><fpage>310</fpage><lpage>314</lpage><pub-id pub-id-type="pmid">9133961</pub-id></element-citation></ref><ref id="R19"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hoffman</surname><given-names>RW</given-names></name><name><surname>O’Sullivan</surname><given-names>FX</given-names></name><name><surname>Schafermeyer</surname><given-names>KR</given-names></name><name><surname>Moore</surname><given-names>TL</given-names></name><name><surname>Roussell</surname><given-names>D</given-names></name><etal></etal></person-group><year>1997</year><article-title>Mycoplasma infection and rheumatoid arthritis: analysis of their relationship using immunoblotting and an ultrasensitive polymerase chain reaction detection method</article-title><source>Arthritis Rheum</source><volume>40</volume><fpage>1219</fpage><lpage>1228</lpage><pub-id pub-id-type="pmid">9214421</pub-id></element-citation></ref><ref id="R20"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Saal</surname><given-names>JG</given-names></name><name><surname>Steidle</surname><given-names>M</given-names></name><name><surname>Einsele</surname><given-names>H</given-names></name><name><surname>Müller</surname><given-names>CA</given-names></name><name><surname>Fritz</surname><given-names>P</given-names></name><etal></etal></person-group><year>1992</year><article-title>Persistence of B19 parvovirus in synovial membranes of patients with rheumatoid arthritis</article-title><source>Rheumatol Int</source><volume>12</volume><fpage>147</fpage><lpage>151</lpage><pub-id pub-id-type="pmid">1439481</pub-id></element-citation></ref><ref id="R21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Takeda</surname><given-names>T</given-names></name><name><surname>Mizugaki</surname><given-names>Y</given-names></name><name><surname>Matsubara</surname><given-names>L</given-names></name><name><surname>Imai</surname><given-names>S</given-names></name><name><surname>Koike</surname><given-names>T</given-names></name><etal></etal></person-group><year>2000</year><article-title>Lytic Epstein-Barr virus infection in the synovial tissue of patients with rheumatoid arthritis</article-title><source>Arthritis Rheum</source><volume>43</volume><fpage>1218</fpage><lpage>1225</lpage><pub-id pub-id-type="pmid">10857780</pub-id></element-citation></ref><ref id="R22"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mehraein</surname><given-names>Y</given-names></name><name><surname>Lennerz</surname><given-names>C</given-names></name><name><surname>Ehlhardt</surname><given-names>S</given-names></name><name><surname>Remberger</surname><given-names>K</given-names></name><name><surname>Ojak</surname><given-names>A</given-names></name><etal></etal></person-group><year>2004</year><article-title>Latent Epstein-Barr virus (EBV) infection and cytomegalovirus (CMV) infection in synovial tissue of autoimmune chronic arthritis determined by RNA- and DNA-in situ hybridization</article-title><source>Mod Pathol</source><volume>17</volume><fpage>781</fpage><lpage>789</lpage><pub-id pub-id-type="pmid">15044921</pub-id></element-citation></ref><ref id="R23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tamm</surname><given-names>A</given-names></name><name><surname>Ziegler</surname><given-names>T</given-names></name><name><surname>Lautenschlager</surname><given-names>I</given-names></name><name><surname>Nikkari</surname><given-names>S</given-names></name><name><surname>Möttönen</surname><given-names>T</given-names></name><etal></etal></person-group><year>1993</year><article-title>Detection of cytomegalovirus DNA in cells from synovial fluid and peripheral blood of patients with early rheumatoid arthritis</article-title><source>J Rheumatol</source><volume>20</volume><fpage>1489</fpage><lpage>1493</lpage><pub-id pub-id-type="pmid">8164203</pub-id></element-citation></ref><ref id="R24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Newkirk</surname><given-names>MM</given-names></name><name><surname>Watanabe Duffy</surname><given-names>KN</given-names></name><name><surname>Leclerc</surname><given-names>J</given-names></name><name><surname>Lambert</surname><given-names>N</given-names></name><name><surname>Shiroky</surname><given-names>JB</given-names></name></person-group><year>1994</year><article-title>Detection of cytomegalovirus, Epstein-Barr virus and herpes virus-6 in patients with rheumatoid arthritis with or without Sjögren’s syndrome</article-title><source>Br J Rheumatol</source><volume>33</volume><fpage>317</fpage><lpage>322</lpage><pub-id pub-id-type="pmid">8156301</pub-id></element-citation></ref><ref id="R25"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>L</given-names></name><name><surname>Nikkari</surname><given-names>S</given-names></name><name><surname>Skurnik</surname><given-names>M</given-names></name><name><surname>Ziegler</surname><given-names>T</given-names></name><name><surname>Luukkainen</surname><given-names>R</given-names></name><etal></etal></person-group><year>1993</year><article-title>Detection of herpesviruses by polymerase chain reaction in lymphocytes from patients with rheumatoid arthritis</article-title><source>Arthritis Rheum</source><volume>36</volume><fpage>1080</fpage><lpage>1086</lpage><pub-id pub-id-type="pmid">8343184</pub-id></element-citation></ref><ref id="R26"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van der Heijden</surname><given-names>IM</given-names></name><name><surname>Wilbrink</surname><given-names>B</given-names></name><name><surname>Tchetverikov</surname><given-names>I</given-names></name><name><surname>Schrijver</surname><given-names>IA</given-names></name><name><surname>Schouls</surname><given-names>LM</given-names></name><etal></etal></person-group><year>2000</year><article-title>Presence of bacterial DNA and bacterial peptidoglycans in joints of patients with rheumatoid arthritis and other arthritides</article-title><source>Arthritis Rheum</source><volume>43</volume><fpage>593</fpage><lpage>598</lpage><pub-id pub-id-type="pmid">10728753</pub-id></element-citation></ref><ref id="R27"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>T</given-names></name><name><surname>Rimpilainen</surname><given-names>M</given-names></name><name><surname>Luukkainen</surname><given-names>R</given-names></name><name><surname>Mottonen</surname><given-names>T</given-names></name><name><surname>Yli-Jama</surname><given-names>T</given-names></name><etal></etal></person-group><year>2003</year><article-title>Bacterial components in the synovial tissue of patients with advanced rheumatoid arthritis or osteoarthritis: analysis with gas chromatography-mass spectrometry and pan-bacterial polymerase chain reaction</article-title><source>Arthritis Rheum</source><volume>49</volume><fpage>328</fpage><lpage>334</lpage><pub-id pub-id-type="pmid">12794787</pub-id></element-citation></ref><ref id="R28"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eerola</surname><given-names>E</given-names></name><name><surname>Möttönen</surname><given-names>T</given-names></name><name><surname>Hannonen</surname><given-names>P</given-names></name><name><surname>Luukkainen</surname><given-names>R</given-names></name><name><surname>Kantola</surname><given-names>I</given-names></name><etal></etal></person-group><year>1994</year><article-title>Intestinal flora in early rheumatoid arthritis</article-title><source>Br J Rheumatol</source><volume>33</volume><fpage>1030</fpage><lpage>1038</lpage><pub-id pub-id-type="pmid">7981990</pub-id></element-citation></ref><ref id="R29"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kawahito</surname><given-names>Y</given-names></name><name><surname>Ichinose</surname><given-names>S</given-names></name><name><surname>Sano</surname><given-names>H</given-names></name><name><surname>Tsubouchi</surname><given-names>Y</given-names></name><name><surname>Kohno</surname><given-names>M</given-names></name><etal></etal></person-group><year>2008</year><article-title>Mycoplasma fermentans glycolipid-antigen as a pathogen of rheumatoid arthritis</article-title><source>Biochem Biophys Res Commun</source><volume>369</volume><fpage>561</fpage><lpage>566</lpage><pub-id pub-id-type="pmid">18307980</pub-id></element-citation></ref><ref id="R30"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Newkirk</surname><given-names>MM</given-names></name><name><surname>Goldbach-Mansky</surname><given-names>R</given-names></name><name><surname>Senior</surname><given-names>BW</given-names></name><name><surname>Klippel</surname><given-names>J</given-names></name><name><surname>Schumacher</surname><given-names>HR</given-names><suffix>Jr</suffix></name><etal></etal></person-group><year>2005</year><article-title>Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis</article-title><source>Rheumatology (Oxford)</source><volume>44</volume><fpage>1433</fpage><lpage>1441</lpage><pub-id pub-id-type="pmid">16091399</pub-id></element-citation></ref><ref id="R31"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kjeldsen-Kragh</surname><given-names>J</given-names></name><name><surname>Rashid</surname><given-names>T</given-names></name><name><surname>Dybwad</surname><given-names>A</given-names></name><name><surname>Sioud</surname><given-names>M</given-names></name><name><surname>Haugen</surname><given-names>M</given-names></name><etal></etal></person-group><year>1995</year><article-title>Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet</article-title><source>Ann Rheum Dis</source><volume>54</volume><fpage>221</fpage><lpage>224</lpage><pub-id pub-id-type="pmid">7748020</pub-id></element-citation></ref><ref id="R32"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tiwana</surname><given-names>H</given-names></name><name><surname>Wilson</surname><given-names>C</given-names></name><name><surname>Alvarez</surname><given-names>A</given-names></name><name><surname>Abuknesha</surname><given-names>R</given-names></name><name><surname>Bansal</surname><given-names>S</given-names></name><etal></etal></person-group><year>1999</year><article-title>Cross-reactivity between the rheumatoid arthritis-associated motif EQKRAA and structurally related sequences found in Proteus mirabilis</article-title><source>Infect Immun</source><volume>67</volume><fpage>2769</fpage><lpage>2775</lpage><pub-id pub-id-type="pmid">10338479</pub-id></element-citation></ref><ref id="R33"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rashid</surname><given-names>T</given-names></name><name><surname>Jayakumar</surname><given-names>KS</given-names></name><name><surname>Binder</surname><given-names>A</given-names></name><name><surname>Ellis</surname><given-names>S</given-names></name><name><surname>Cunningham</surname><given-names>P</given-names></name><etal></etal></person-group><year>2007</year><article-title>Rheumatoid arthritis patients have elevated antibodies to cross-reactive and non cross-reactive antigens from Proteus microbes</article-title><source>Clin Exp Rheumatol</source><volume>25</volume><fpage>259</fpage><lpage>267</lpage><pub-id pub-id-type="pmid">17543151</pub-id></element-citation></ref><ref id="R34"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hitchon</surname><given-names>CA</given-names></name><name><surname>Chandad</surname><given-names>F</given-names></name><name><surname>Ferucci</surname><given-names>ED</given-names></name><name><surname>Willemze</surname><given-names>A</given-names></name><name><surname>Ioan-Facsinay</surname><given-names>A</given-names></name><etal></etal></person-group><year>2010</year><article-title>Antibodies to porphyromonas gingivalis are associated with anticitrullinated protein antibodies in patients with rheumatoid arthritis and their relatives</article-title><source>J Rheumatol</source><volume>37</volume><fpage>1105</fpage><lpage>1112</lpage><pub-id pub-id-type="pmid">20436074</pub-id></element-citation></ref><ref id="R35"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mikuls</surname><given-names>TR</given-names></name><name><surname>Payne</surname><given-names>JB</given-names></name><name><surname>Reinhardt</surname><given-names>RA</given-names></name><name><surname>Thiele</surname><given-names>GM</given-names></name><name><surname>Maziarz</surname><given-names>E</given-names></name><etal></etal></person-group><year>2009</year><article-title>Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis</article-title><source>Int Immunopharmacol</source><volume>9</volume><fpage>38</fpage><lpage>42</lpage><pub-id pub-id-type="pmid">18848647</pub-id></element-citation></ref><ref id="R36"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mikuls</surname><given-names>TR</given-names></name><name><surname>Thiele</surname><given-names>GM</given-names></name><name><surname>Deane</surname><given-names>KD</given-names></name><name><surname>Payne</surname><given-names>JB</given-names></name><name><surname>O’Dell</surname><given-names>JR</given-names></name><etal></etal></person-group><year>2012</year><article-title>Porphyromonas gingivalis and disease-related autoantibodies in individuals at increased risk of rheumatoid arthritis</article-title><source>Arthritis Rheum</source><volume>64</volume><fpage>3522</fpage><lpage>3530</lpage><pub-id pub-id-type="pmid">22736291</pub-id></element-citation></ref><ref id="R37"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Blaschke</surname><given-names>S</given-names></name><name><surname>Schwarz</surname><given-names>G</given-names></name><name><surname>Moneke</surname><given-names>D</given-names></name><name><surname>Binder</surname><given-names>L</given-names></name><name><surname>Müller</surname><given-names>G</given-names></name><etal></etal></person-group><year>2000</year><article-title>Epstein-Barr virus infection in peripheral blood mononuclear cells, synovial fluid cells, and synovial membranes of patients with rheumatoid arthritis</article-title><source>J Rheumatol</source><volume>27</volume><fpage>866</fpage><lpage>873</lpage><pub-id pub-id-type="pmid">10782808</pub-id></element-citation></ref><ref id="R38"><label>38</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tzang</surname><given-names>BS</given-names></name><name><surname>Tsai</surname><given-names>CC</given-names></name><name><surname>Tsay</surname><given-names>GJ</given-names></name><name><surname>Wang</surname><given-names>M</given-names></name><name><surname>Sun</surname><given-names>YS</given-names></name><etal></etal></person-group><year>2009</year><article-title>Anti-human parvovirus B19 nonstructural protein antibodies in patients with rheumatoid arthritis</article-title><source>Clin Chim Acta</source><volume>405</volume><fpage>76</fpage><lpage>82</lpage><pub-id pub-id-type="pmid">19362081</pub-id></element-citation></ref><ref id="R39"><label>39</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>da Rocha Sobrinho</surname><given-names>HM</given-names></name><name><surname>Jarach</surname><given-names>R</given-names></name><name><surname>da Silva</surname><given-names>NA</given-names></name><name><surname>Shio</surname><given-names>MT</given-names></name><name><surname>Jancar</surname><given-names>S</given-names></name><etal></etal></person-group><year>2011</year><article-title>Mycoplasmal lipid-associated membrane proteins and Mycoplasma arthritidis mitogen recognition by serum antibodies from patients with rheumatoid arthritis</article-title><source>Rheumatol Int</source><volume>31</volume><fpage>951</fpage><lpage>957</lpage><pub-id pub-id-type="pmid">21052674</pub-id></element-citation></ref><ref id="R40"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sawitzke</surname><given-names>A</given-names></name><name><surname>Joyner</surname><given-names>D</given-names></name><name><surname>Knudtson</surname><given-names>K</given-names></name><name><surname>Mu</surname><given-names>HH</given-names></name><name><surname>Cole</surname><given-names>B</given-names></name></person-group><year>2000</year><article-title>Anti-MAM antibodies in rheumatic disease: evidence for a MAM-like superantigen in rheumatoid arthritis?</article-title><source>J Rheumatol</source><volume>27</volume><fpage>358</fpage><lpage>364</lpage><pub-id pub-id-type="pmid">10685797</pub-id></element-citation></ref><ref id="R41"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Scotet</surname><given-names>E</given-names></name><name><surname>David-Ameline</surname><given-names>J</given-names></name><name><surname>Peyrat</surname><given-names>MA</given-names></name><name><surname>Moreau-Aubry</surname><given-names>A</given-names></name><name><surname>Pinczon</surname><given-names>D</given-names></name><etal></etal></person-group><year>1996</year><article-title>T cell response to Epstein-Barr virus transactivators in chronic rheumatoid arthritis</article-title><source>J Exp Med</source><volume>184</volume><fpage>1791</fpage><lpage>1800</lpage><pub-id pub-id-type="pmid">8920867</pub-id></element-citation></ref><ref id="R42"><label>42</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lunemann</surname><given-names>JD</given-names></name><name><surname>Frey</surname><given-names>O</given-names></name><name><surname>Eidner</surname><given-names>T</given-names></name><name><surname>Baier</surname><given-names>M</given-names></name><name><surname>Roberts</surname><given-names>S</given-names></name><etal></etal></person-group><year>2008</year><article-title>Increased frequency of EBV-specific effector memory CD8+ T cells correlates with higher viral load in rheumatoid arthritis</article-title><source>J Immunol</source><volume>181</volume><fpage>991</fpage><lpage>1000</lpage><pub-id pub-id-type="pmid">18606650</pub-id></element-citation></ref><ref id="R43"><label>43</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Klatt</surname><given-names>T</given-names></name><name><surname>Ouyang</surname><given-names>Q</given-names></name><name><surname>Flad</surname><given-names>T</given-names></name><name><surname>Koetter</surname><given-names>I</given-names></name><name><surname>Bühring</surname><given-names>HJ</given-names></name><etal></etal></person-group><year>2005</year><article-title>Expansion of peripheral CD8+ CD28− T cells in response to Epstein-Barr virus in patients with rheumatoid arthritis</article-title><source>J Rheumatol</source><volume>32</volume><fpage>239</fpage><lpage>251</lpage><pub-id pub-id-type="pmid">15693083</pub-id></element-citation></ref><ref id="R44"><label>44</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ford</surname><given-names>DK</given-names></name><name><surname>da Roza</surname><given-names>DM</given-names></name><name><surname>Schulzer</surname><given-names>M</given-names></name><name><surname>Reid</surname><given-names>GD</given-names></name><name><surname>Denegri</surname><given-names>JF</given-names></name></person-group><year>1987</year><article-title>Persistent synovial lymphocyte responses to cytomegalovirus antigen in some patients with rheumatoid arthritis</article-title><source>Arthritis Rheum</source><volume>30</volume><fpage>700</fpage><lpage>704</lpage><pub-id pub-id-type="pmid">3038132</pub-id></element-citation></ref><ref id="R45"><label>45</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Doran</surname><given-names>MF</given-names></name><name><surname>Gabriel</surname><given-names>SE</given-names></name></person-group><year>2001</year><article-title>Infections in rheumatoid arthritis--a new phenomenon?</article-title><source>J Rheumatol</source><volume>28</volume><fpage>1942</fpage><lpage>1943</lpage><pub-id pub-id-type="pmid">11550957</pub-id></element-citation></ref><ref id="R46"><label>46</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cole</surname><given-names>BC</given-names></name><name><surname>Golightly-Rowland</surname><given-names>L</given-names></name><name><surname>Ward</surname><given-names>JR</given-names></name></person-group><year>1976</year><article-title>Arthritis of mice induced by Mycoplasma arthritidis. Humoral antibody and lymphocyte responses of CBA mice</article-title><source>Ann Rheum Dis</source><volume>35</volume><fpage>14</fpage><lpage>22</lpage><pub-id pub-id-type="pmid">1275576</pub-id></element-citation></ref><ref id="R47"><label>47</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bartold</surname><given-names>PM</given-names></name><name><surname>Marino</surname><given-names>V</given-names></name><name><surname>Cantley</surname><given-names>M</given-names></name><name><surname>Haynes</surname><given-names>DR</given-names></name></person-group><year>2010</year><article-title>Effect of Porphyromonas gingivalis-induced inflammation on the development of rheumatoid arthritis</article-title><source>J Clin Periodontol</source><volume>37</volume><fpage>405</fpage><lpage>411</lpage><pub-id pub-id-type="pmid">20507365</pub-id></element-citation></ref><ref id="R48"><label>48</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kinloch</surname><given-names>AJ</given-names></name><name><surname>Alzabin</surname><given-names>S</given-names></name><name><surname>Brintnell</surname><given-names>W</given-names></name><name><surname>Wilson</surname><given-names>E</given-names></name><name><surname>Barra</surname><given-names>L</given-names></name><etal></etal></person-group><year>2011</year><article-title>Immunization with Porphyromonas gingivalis enolase induces autoimmunity to mammalian α-enolase and arthritis in DR4-IE-transgenic mice</article-title><source>Arthritis Rheum</source><volume>63</volume><fpage>3818</fpage><lpage>3823</lpage><pub-id pub-id-type="pmid">21953289</pub-id></element-citation></ref><ref id="R49"><label>49</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cantley</surname><given-names>MD</given-names></name><name><surname>Haynes</surname><given-names>DR</given-names></name><name><surname>Marino</surname><given-names>V</given-names></name><name><surname>Bartold</surname><given-names>PM</given-names></name></person-group><year>2011</year><article-title>Pre-existing periodontitis exacerbates experimental arthritis in a mouse model</article-title><source>J Clin Periodontol</source><volume>38</volume><fpage>532</fpage><lpage>541</lpage><pub-id pub-id-type="pmid">21434962</pub-id></element-citation></ref><ref id="R50"><label>50</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cole</surname><given-names>BC</given-names></name><name><surname>Griffiths</surname><given-names>MM</given-names></name></person-group><year>1993</year><article-title>Triggering and exacerbation of autoimmune arthritis by the Mycoplasma arthritidis superantigen MAM</article-title><source>Arthritis Rheum</source><volume>36</volume><fpage>994</fpage><lpage>1002</lpage><pub-id pub-id-type="pmid">8318046</pub-id></element-citation></ref><ref id="R51"><label>51</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Maresz</surname><given-names>KJ</given-names></name><name><surname>Hellvard</surname><given-names>A</given-names></name><name><surname>Sroka</surname><given-names>A</given-names></name><name><surname>Adamowicz</surname><given-names>K</given-names></name><name><surname>Bielecka</surname><given-names>E</given-names></name><etal></etal></person-group><year>2013</year><article-title>Porphyromonas gingivalis facilitates the development and progression of destructive arthritis through its unique bacterial peptidylarginine deiminase (PAD)</article-title><source>PLoS Pathog</source><volume>9</volume><fpage>e1003627</fpage><pub-id pub-id-type="pmid">24068934</pub-id></element-citation></ref><ref id="R52"><label>52</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wu</surname><given-names>HJ</given-names></name><name><surname>Ivanov</surname><given-names>II</given-names></name><name><surname>Darce</surname><given-names>J</given-names></name><name><surname>Hattori</surname><given-names>K</given-names></name><name><surname>Shima</surname><given-names>T</given-names></name><etal></etal></person-group><year>2010</year><article-title>Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells</article-title><source>Immunity</source><volume>32</volume><fpage>815</fpage><lpage>827</lpage><pub-id pub-id-type="pmid">20620945</pub-id></element-citation></ref><ref id="R53"><label>53</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Simelyte</surname><given-names>E</given-names></name><name><surname>Rimpiläinen</surname><given-names>M</given-names></name><name><surname>Zhang</surname><given-names>X</given-names></name><name><surname>Toivanen</surname><given-names>P</given-names></name></person-group><year>2003</year><article-title>Role of peptidoglycan subtypes in the pathogenesis of bacterial cell wall arthritis</article-title><source>Ann Rheum Dis</source><volume>62</volume><fpage>976</fpage><lpage>982</lpage><pub-id pub-id-type="pmid">12972477</pub-id></element-citation></ref><ref id="R54"><label>54</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Caccese</surname><given-names>RG</given-names></name><name><surname>Zimmerman</surname><given-names>JL</given-names></name><name><surname>Carlson</surname><given-names>RP</given-names></name></person-group><year>1992</year><article-title>Bacterial lipopolysaccharide potentiates type II collagen-induced arthritis in mice</article-title><source>Mediators Inflamm</source><volume>1</volume><fpage>273</fpage><lpage>279</lpage><pub-id pub-id-type="pmid">18475473</pub-id></element-citation></ref><ref id="R55"><label>55</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kuwana</surname><given-names>Y</given-names></name><name><surname>Takei</surname><given-names>M</given-names></name><name><surname>Yajima</surname><given-names>M</given-names></name><name><surname>Imadome</surname><given-names>K</given-names></name><name><surname>Inomata</surname><given-names>H</given-names></name><etal></etal></person-group><year>2011</year><article-title>Epstein-Barr virus induces erosive arthritis in humanized mice</article-title><source>PLoS One</source><volume>6</volume><fpage>e26630</fpage><pub-id pub-id-type="pmid">22028930</pub-id></element-citation></ref><ref id="R56"><label>56</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Warde</surname><given-names>N</given-names></name></person-group><year>2011</year><article-title>Experimental arthritis: EBV induces arthritis in mice</article-title><source>Nat Rev Rheumatol</source><volume>7</volume><fpage>683</fpage><pub-id pub-id-type="pmid">22083222</pub-id></element-citation></ref><ref id="R57"><label>57</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Iwakura</surname><given-names>Y</given-names></name><name><surname>Tosu</surname><given-names>M</given-names></name><name><surname>Yoshida</surname><given-names>E</given-names></name><name><surname>Takiguchi</surname><given-names>M</given-names></name><name><surname>Sato</surname><given-names>K</given-names></name><etal></etal></person-group><year>1991</year><article-title>Induction of inflammatory arthropathy resembling rheumatoid arthritis in mice transgenic for HTLV-I</article-title><source>Science</source><volume>253</volume><fpage>1026</fpage><lpage>1028</lpage><pub-id pub-id-type="pmid">1887217</pub-id></element-citation></ref><ref id="R58"><label>58</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aletaha</surname><given-names>D</given-names></name><name><surname>Neogi</surname><given-names>T</given-names></name><name><surname>Silman</surname><given-names>AJ</given-names></name><name><surname>Funovits</surname><given-names>J</given-names></name><name><surname>Felson</surname><given-names>DT</given-names></name><etal></etal></person-group><year>2010</year><article-title>2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative</article-title><source>Arthritis Rheum</source><volume>62</volume><fpage>2569</fpage><lpage>2581</lpage><pub-id pub-id-type="pmid">20872595</pub-id></element-citation></ref><ref id="R59"><label>59</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aletaha</surname><given-names>D</given-names></name><name><surname>Neogi</surname><given-names>T</given-names></name><name><surname>Silman</surname><given-names>AJ</given-names></name><name><surname>Funovits</surname><given-names>J</given-names></name><name><surname>Felson</surname><given-names>DT</given-names></name><etal></etal></person-group><year>2010</year><article-title>2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative</article-title><source>Ann Rheum Dis</source><volume>69</volume><fpage>1580</fpage><lpage>1588</lpage><pub-id pub-id-type="pmid">20699241</pub-id></element-citation></ref><ref id="R60"><label>60</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van de Stadt</surname><given-names>LA</given-names></name><name><surname>de Koning</surname><given-names>MH</given-names></name><name><surname>van de Stadt</surname><given-names>RJ</given-names></name><name><surname>Wolbink</surname><given-names>G</given-names></name><name><surname>Dijkmans</surname><given-names>BA</given-names></name><etal></etal></person-group><year>2011</year><article-title>Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis</article-title><source>Arthritis Rheum</source><volume>63</volume><fpage>3226</fpage><lpage>3233</lpage><pub-id pub-id-type="pmid">21792832</pub-id></element-citation></ref><ref id="R61"><label>61</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wegner</surname><given-names>N</given-names></name><name><surname>Lundberg</surname><given-names>K</given-names></name><name><surname>Kinloch</surname><given-names>A</given-names></name><name><surname>Fisher</surname><given-names>B</given-names></name><name><surname>Malmström</surname><given-names>V</given-names></name><etal></etal></person-group><year>2010</year><article-title>Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis</article-title><source>Immunol Rev</source><volume>233</volume><fpage>34</fpage><lpage>54</lpage><pub-id pub-id-type="pmid">20192991</pub-id></element-citation></ref><ref id="R62"><label>62</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wegner</surname><given-names>N</given-names></name><name><surname>Wait</surname><given-names>R</given-names></name><name><surname>Sroka</surname><given-names>A</given-names></name><name><surname>Eick</surname><given-names>S</given-names></name><name><surname>Nguyen</surname><given-names>KA</given-names></name><etal></etal></person-group><year>2010</year><article-title>Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and alpha-enolase: implications for autoimmunity in rheumatoid arthritis</article-title><source>Arthritis Rheum</source><volume>62</volume><fpage>2662</fpage><lpage>2672</lpage><pub-id pub-id-type="pmid">20506214</pub-id></element-citation></ref><ref id="R63"><label>63</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vossenaar</surname><given-names>ER</given-names></name><name><surname>Radstake</surname><given-names>TR</given-names></name><name><surname>van der Heijden</surname><given-names>A</given-names></name><name><surname>van Mansum</surname><given-names>MA</given-names></name><name><surname>Dieteren</surname><given-names>C</given-names></name><etal></etal></person-group><year>2004</year><article-title>Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages</article-title><source>Ann Rheum Dis</source><volume>63</volume><fpage>373</fpage><lpage>381</lpage><pub-id pub-id-type="pmid">15020330</pub-id></element-citation></ref><ref id="R64"><label>64</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Foulquier</surname><given-names>C</given-names></name><name><surname>Sebbag</surname><given-names>M</given-names></name><name><surname>Clavel</surname><given-names>C</given-names></name><name><surname>Chapuy-Regaud</surname><given-names>S</given-names></name><name><surname>Al Badine</surname><given-names>R</given-names></name><etal></etal></person-group><year>2007</year><article-title>Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation</article-title><source>Arthritis Rheum</source><volume>56</volume><fpage>3541</fpage><lpage>3553</lpage><pub-id pub-id-type="pmid">17968929</pub-id></element-citation></ref><ref id="R65"><label>65</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mangat</surname><given-names>P</given-names></name><name><surname>Wegner</surname><given-names>N</given-names></name><name><surname>Venables</surname><given-names>PJ</given-names></name><name><surname>Potempa</surname><given-names>J</given-names></name></person-group><year>2010</year><article-title>Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune response in rheumatoid arthritis?</article-title><source>Arthritis Res Ther</source><volume>12</volume><fpage>209</fpage><pub-id pub-id-type="pmid">20553633</pub-id></element-citation></ref><ref id="R66"><label>66</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yu</surname><given-names>Y</given-names></name><name><surname>Su</surname><given-names>K</given-names></name></person-group><year>2013</year><article-title>Neutrophil Extracellular Traps and Systemic Lupus Erythematosus</article-title><source>J Clin Cell Immunol</source><volume>4</volume><fpage>139</fpage><pub-id pub-id-type="pmid">24244889</pub-id></element-citation></ref><ref id="R67"><label>67</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Khandpur</surname><given-names>R</given-names></name><name><surname>Carmona-Rivera</surname><given-names>C</given-names></name><name><surname>Vivekanandan-Giri</surname><given-names>A</given-names></name><name><surname>Gizinski</surname><given-names>A</given-names></name><name><surname>Yalavarthi</surname><given-names>S</given-names></name><etal></etal></person-group><year>2013</year><article-title>NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis</article-title><source>Sci Transl Med</source><volume>5</volume><fpage>178ra40</fpage></element-citation></ref><ref id="R68"><label>68</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lundberg</surname><given-names>K</given-names></name><name><surname>Nijenhuis</surname><given-names>S</given-names></name><name><surname>Vossenaar</surname><given-names>ER</given-names></name><name><surname>Palmblad</surname><given-names>K</given-names></name><name><surname>van Venrooij</surname><given-names>WJ</given-names></name><etal></etal></person-group><year>2005</year><article-title>Citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity</article-title><source>Arthritis Res Ther</source><volume>7</volume><fpage>R458</fpage><lpage>467</lpage><pub-id pub-id-type="pmid">15899032</pub-id></element-citation></ref><ref id="R69"><label>69</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lundberg</surname><given-names>K</given-names></name><name><surname>Kinloch</surname><given-names>A</given-names></name><name><surname>Fisher</surname><given-names>BA</given-names></name><name><surname>Wegner</surname><given-names>N</given-names></name><name><surname>Wait</surname><given-names>R</given-names></name><etal></etal></person-group><year>2008</year><article-title>Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase</article-title><source>Arthritis Rheum</source><volume>58</volume><fpage>3009</fpage><lpage>3019</lpage><pub-id pub-id-type="pmid">18821669</pub-id></element-citation></ref><ref id="R70"><label>70</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Birkenfeld</surname><given-names>P</given-names></name><name><surname>Haratz</surname><given-names>N</given-names></name><name><surname>Klein</surname><given-names>G</given-names></name><name><surname>Sulitzeanu</surname><given-names>D</given-names></name></person-group><year>1990</year><article-title>Cross-reactivity between the EBNA-1 p107 peptide, collagen, and keratin: implications for the pathogenesis of rheumatoid arthritis</article-title><source>Clin Immunol Immunopathol</source><volume>54</volume><fpage>14</fpage><lpage>25</lpage><pub-id pub-id-type="pmid">1688406</pub-id></element-citation></ref><ref id="R71"><label>71</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Albani</surname><given-names>S</given-names></name><name><surname>Keystone</surname><given-names>EC</given-names></name><name><surname>Nelson</surname><given-names>JL</given-names></name><name><surname>Ollier</surname><given-names>WE</given-names></name><name><surname>La Cava</surname><given-names>A</given-names></name><etal></etal></person-group><year>1995</year><article-title>Positive selection in autoimmunity: abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis</article-title><source>Nat Med</source><volume>1</volume><fpage>448</fpage><lpage>452</lpage><pub-id pub-id-type="pmid">7585093</pub-id></element-citation></ref><ref id="R72"><label>72</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wilson</surname><given-names>C</given-names></name><name><surname>Tiwana</surname><given-names>H</given-names></name><name><surname>Ebringer</surname><given-names>A</given-names></name></person-group><year>2000</year><article-title>Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the Aetiological basis for autoimmunity</article-title><source>Microbes Infect</source><volume>2</volume><fpage>1489</fpage><lpage>1496</lpage><pub-id pub-id-type="pmid">11099935</pub-id></element-citation></ref><ref id="R73"><label>73</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kogure</surname><given-names>A</given-names></name><name><surname>Miyata</surname><given-names>M</given-names></name><name><surname>Nishimaki</surname><given-names>T</given-names></name><name><surname>Kasukawa</surname><given-names>R</given-names></name></person-group><year>1994</year><article-title>Proliferative response of synovial fluid mononuclear cells of patients with rheumatoid arthritis to mycobacterial 65 kDa heat shock protein and its association with HLA-DR+. gamma delta+ T cells</article-title><source>J Rheumatol</source><volume>21</volume><fpage>1403</fpage><lpage>1408</lpage><pub-id pub-id-type="pmid">7983638</pub-id></element-citation></ref><ref id="R74"><label>74</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Celis</surname><given-names>L</given-names></name><name><surname>Vandevyver</surname><given-names>C</given-names></name><name><surname>Geusens</surname><given-names>P</given-names></name><name><surname>Dequeker</surname><given-names>J</given-names></name><name><surname>Raus</surname><given-names>J</given-names></name><etal></etal></person-group><year>1997</year><article-title>Clonal expansion of mycobacterial heat-shock protein-reactive T lymphocytes in the synovial fluid and blood of rheumatoid arthritis patients</article-title><source>Arthritis Rheum</source><volume>40</volume><fpage>510</fpage><lpage>519</lpage><pub-id pub-id-type="pmid">9082939</pub-id></element-citation></ref><ref id="R75"><label>75</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sfriso</surname><given-names>P</given-names></name><name><surname>Ghirardello</surname><given-names>A</given-names></name><name><surname>Botsios</surname><given-names>C</given-names></name><name><surname>Tonon</surname><given-names>M</given-names></name><name><surname>Zen</surname><given-names>M</given-names></name><etal></etal></person-group><year>2010</year><article-title>Infections and autoimmunity: the multifaceted relationship</article-title><source>J Leukoc Biol</source><volume>87</volume><fpage>385</fpage><lpage>395</lpage><pub-id pub-id-type="pmid">20015961</pub-id></element-citation></ref><ref id="R76"><label>76</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barksby</surname><given-names>HE</given-names></name><name><surname>Nile</surname><given-names>CJ</given-names></name><name><surname>Jaedicke</surname><given-names>KM</given-names></name><name><surname>Taylor</surname><given-names>JJ</given-names></name><name><surname>Preshaw</surname><given-names>PM</given-names></name></person-group><year>2009</year><article-title>Differential expression of immunoregulatory genes in monocytes in response to Porphyromonas gingivalis and Escherichia coli lipopolysaccharide</article-title><source>Clin Exp Immunol</source><volume>156</volume><fpage>479</fpage><lpage>487</lpage><pub-id pub-id-type="pmid">19438601</pub-id></element-citation></ref><ref id="R77"><label>77</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nile</surname><given-names>CJ</given-names></name><name><surname>Barksby</surname><given-names>E</given-names></name><name><surname>Jitprasertwong</surname><given-names>P</given-names></name><name><surname>Preshaw</surname><given-names>PM</given-names></name><name><surname>Taylor</surname><given-names>JJ</given-names></name></person-group><year>2010</year><article-title>Expression and regulation of interleukin-33 in human monocytes</article-title><source>Immunology</source><volume>130</volume><fpage>172</fpage><lpage>180</lpage><pub-id pub-id-type="pmid">20070408</pub-id></element-citation></ref><ref id="R78"><label>78</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dziarski</surname><given-names>R</given-names></name></person-group><year>1982</year><article-title>Preferential induction of autoantibody secretion in polyclonal activation by peptidoglycan and lipopolysaccharide. II. In vivo studies</article-title><source>J Immunol</source><volume>128</volume><fpage>1026</fpage><lpage>1030</lpage><pub-id pub-id-type="pmid">7035554</pub-id></element-citation></ref><ref id="R79"><label>79</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>JE</given-names></name><name><surname>Jørgensen</surname><given-names>PF</given-names></name><name><surname>Ellingsen</surname><given-names>EA</given-names></name><name><surname>Almiöf</surname><given-names>M</given-names></name><name><surname>Thiemermann</surname><given-names>C</given-names></name><etal></etal></person-group><year>2001</year><article-title>Peptidoglycan primes for LPS-induced release of proinflammatory cytokines in whole human blood</article-title><source>Shock</source><volume>16</volume><fpage>178</fpage><lpage>182</lpage><pub-id pub-id-type="pmid">11531018</pub-id></element-citation></ref><ref id="R80"><label>80</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Paliard</surname><given-names>X</given-names></name><name><surname>West</surname><given-names>SG</given-names></name><name><surname>Lafferty</surname><given-names>JA</given-names></name><name><surname>Clements</surname><given-names>JR</given-names></name><name><surname>Kappler</surname><given-names>JW</given-names></name><etal></etal></person-group><year>1991</year><article-title>Evidence for the effects of a superantigen in rheumatoid arthritis</article-title><source>Science</source><volume>253</volume><fpage>325</fpage><lpage>329</lpage><pub-id pub-id-type="pmid">1857971</pub-id></element-citation></ref><ref id="R81"><label>81</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Howell</surname><given-names>MD</given-names></name><name><surname>Diveley</surname><given-names>JP</given-names></name><name><surname>Lundeen</surname><given-names>KA</given-names></name><name><surname>Esty</surname><given-names>A</given-names></name><name><surname>Winters</surname><given-names>ST</given-names></name><etal></etal></person-group><year>1991</year><article-title>Limited T-cell receptor beta-chain heterogeneity among interleukin 2 receptor-positive synovial T cells suggests a role for superantigen in rheumatoid arthritis</article-title><source>Proc Natl Acad Sci U S A</source><volume>88</volume><fpage>10921</fpage><lpage>10925</lpage><pub-id pub-id-type="pmid">1660155</pub-id></element-citation></ref><ref id="R82"><label>82</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rickinson</surname><given-names>AB</given-names></name><name><surname>Moss</surname><given-names>DJ</given-names></name></person-group><year>1997</year><article-title>Human cytotoxic T lymphocyte responses to Epstein-Barr virus infection</article-title><source>Annu Rev Immunol</source><volume>15</volume><fpage>405</fpage><lpage>431</lpage><pub-id pub-id-type="pmid">9143694</pub-id></element-citation></ref><ref id="R83"><label>83</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hsiao</surname><given-names>FC</given-names></name><name><surname>Lin</surname><given-names>M</given-names></name><name><surname>Tai</surname><given-names>A</given-names></name><name><surname>Chen</surname><given-names>G</given-names></name><name><surname>Huber</surname><given-names>BT</given-names></name></person-group><year>2006</year><article-title>Cutting edge: Epstein-Barr virus transactivates the HERV-K18 superantigen by docking to the human complement receptor 2 (CD21) on primary B cells</article-title><source>J Immunol</source><volume>177</volume><fpage>2056</fpage><lpage>2060</lpage><pub-id pub-id-type="pmid">16887963</pub-id></element-citation></ref><ref id="R84"><label>84</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schwab</surname><given-names>JH</given-names></name><name><surname>Brown</surname><given-names>RR</given-names></name><name><surname>Anderle</surname><given-names>SK</given-names></name><name><surname>Schlievert</surname><given-names>PM</given-names></name></person-group><year>1993</year><article-title>Superantigen can reactivate bacterial cell wall-induced arthritis</article-title><source>J Immunol</source><volume>150</volume><fpage>4151</fpage><lpage>4159</lpage><pub-id pub-id-type="pmid">8473753</pub-id></element-citation></ref><ref id="R85"><label>85</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Okahashi</surname><given-names>N</given-names></name><name><surname>Sakurai</surname><given-names>A</given-names></name><name><surname>Nakagawa</surname><given-names>I</given-names></name><name><surname>Fujiwara</surname><given-names>T</given-names></name><name><surname>Kawabata</surname><given-names>S</given-names></name><etal></etal></person-group><year>2003</year><article-title>Infection by Streptococcus pyogenes induces the receptor activator of NF-kappaB ligand expression in mouse osteoblastic cells</article-title><source>Infect Immun</source><volume>71</volume><fpage>948</fpage><lpage>955</lpage><pub-id pub-id-type="pmid">12540577</pub-id></element-citation></ref><ref id="R86"><label>86</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kotake</surname><given-names>S</given-names></name><name><surname>Udagawa</surname><given-names>N</given-names></name><name><surname>Hakoda</surname><given-names>M</given-names></name><name><surname>Mogi</surname><given-names>M</given-names></name><name><surname>Yano</surname><given-names>K</given-names></name><etal></etal></person-group><year>2001</year><article-title>Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients</article-title><source>Arthritis Rheum</source><volume>44</volume><fpage>1003</fpage><lpage>1012</lpage><pub-id pub-id-type="pmid">11352231</pub-id></element-citation></ref><ref id="R87"><label>87</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>X</given-names></name><name><surname>Aubin</surname><given-names>JE</given-names></name><name><surname>Kim</surname><given-names>TH</given-names></name><name><surname>Payne</surname><given-names>U</given-names></name><name><surname>Chiu</surname><given-names>B</given-names></name><etal></etal></person-group><year>2004</year><article-title>Synovial fibroblasts infected with Salmonella enterica serovar Typhimurium mediate osteoclast differentiation and activation</article-title><source>Infect Immun</source><volume>72</volume><fpage>7183</fpage><lpage>7189</lpage><pub-id pub-id-type="pmid">15557643</pub-id></element-citation></ref><ref id="R88"><label>88</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Röhner</surname><given-names>E</given-names></name><name><surname>Detert</surname><given-names>J</given-names></name><name><surname>Kolar</surname><given-names>P</given-names></name><name><surname>Hocke</surname><given-names>A</given-names></name><name><surname>N’Guessan</surname><given-names>P</given-names></name><etal></etal></person-group><year>2010</year><article-title>Induced apoptosis of chondrocytes by Porphyromonas gingivalis as a possible pathway for cartilage loss in rheumatoid arthritis</article-title><source>Calcif Tissue Int</source><volume>87</volume><fpage>333</fpage><lpage>340</lpage><pub-id pub-id-type="pmid">20582408</pub-id></element-citation></ref><ref id="R89"><label>89</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Roudier</surname><given-names>J</given-names></name><name><surname>Petersen</surname><given-names>J</given-names></name><name><surname>Rhodes</surname><given-names>GH</given-names></name><name><surname>Luka</surname><given-names>J</given-names></name><name><surname>Carson</surname><given-names>DA</given-names></name></person-group><year>1989</year><article-title>Susceptibility to rheumatoid arthritis maps to a T-cell epitope shared by the HLA-Dw4 DR beta-1 chain and the Epstein-Barr virus glycoprotein gp110</article-title><source>Proc Natl Acad Sci U S A</source><volume>86</volume><fpage>5104</fpage><lpage>5108</lpage><pub-id pub-id-type="pmid">2472638</pub-id></element-citation></ref></ref-list></back><floats-group><table-wrap id="T1" position="float" orientation="portrait"><label>Table 1</label><caption><p>Common RA-associated microbes.</p></caption><table frame="box" rules="all"><thead><tr><th valign="bottom" align="left" rowspan="1" colspan="1">Microbes</th><th valign="bottom" align="left" rowspan="1" colspan="1">Clinical association</th><th valign="bottom" align="left" rowspan="1" colspan="1">Animal study</th><th valign="bottom" align="left" rowspan="1" colspan="1">Arthritogenic mechanism</th></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Porphyromonas</td><td align="left" valign="top" rowspan="1" colspan="1">Clinical association between RA and periodontitis [<xref rid="R6" ref-type="bibr">6</xref>–<xref rid="R10" ref-type="bibr">10</xref>].<break></break>Presence of <italic>P. gingivalis</italic> DNA in RA patients [<xref rid="R17" ref-type="bibr">17</xref>].<break></break>Immune responses to <italic>P. gingivalis</italic> in RA patients [<xref rid="R34" ref-type="bibr">34</xref>,<xref rid="R35" ref-type="bibr">35</xref>].<break></break>Increased anti-<italic>P. gingivalis</italic> antibodies in subjects with high risk of RA [<xref rid="R36" ref-type="bibr">36</xref>].</td><td align="left" valign="top" rowspan="1" colspan="1">Immunization with <italic>P. gingivalis</italic> or <italic>P. gingivalis</italic> enolase induced or exacerbated arthritis [<xref rid="R47" ref-type="bibr">47</xref>–<xref rid="R49" ref-type="bibr">49</xref>].<break></break><italic>P. gingivalis</italic> facilitated destructive arthritis in CIA mice dependent on its peptidylarginine deiminase [<xref rid="R51" ref-type="bibr">51</xref>].</td><td align="left" valign="top" rowspan="1" colspan="1">Neo-antigen generation [<xref rid="R62" ref-type="bibr">62</xref>].<break></break>Molecular mimicry [<xref rid="R69" ref-type="bibr">69</xref>].<break></break>Bystander activation [<xref rid="R47" ref-type="bibr">47</xref>,<xref rid="R49" ref-type="bibr">49</xref>].<break></break>Direct joint damage [<xref rid="R88" ref-type="bibr">88</xref>].</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Proteus</td><td align="left" valign="top" rowspan="1" colspan="1">Clinical association between RA and urinary tract infection [<xref rid="R11" ref-type="bibr">11</xref>].<break></break>Immune responses to <italic>P. mirabilis</italic> in RA patients [<xref rid="R30" ref-type="bibr">30</xref>–<xref rid="R33" ref-type="bibr">33</xref>].</td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">Molecular mimicry [<xref rid="R33" ref-type="bibr">33</xref>].</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">EBV</td><td align="left" valign="top" rowspan="1" colspan="1">Clinical association between RA and EBV infection [<xref rid="R24" ref-type="bibr">24</xref>].<break></break>Presence of EBV DNA and protein in RA patients [<xref rid="R21" ref-type="bibr">21</xref>,<xref rid="R22" ref-type="bibr">22</xref>].<break></break>Immune responses to EBV in RA patients [<xref rid="R37" ref-type="bibr">37</xref>,<xref rid="R41" ref-type="bibr">41</xref>–<xref rid="R43" ref-type="bibr">43</xref>].</td><td align="left" valign="top" rowspan="1" colspan="1">EBV induced arthritis in humanized mice [<xref rid="R55" ref-type="bibr">55</xref>,<xref rid="R56" ref-type="bibr">56</xref>].</td><td align="left" valign="top" rowspan="1" colspan="1">Molecular mimicry [<xref rid="R70" ref-type="bibr">70</xref>,<xref rid="R89" ref-type="bibr">89</xref>].<break></break>Superantigen [<xref rid="R43" ref-type="bibr">43</xref>,<xref rid="R82" ref-type="bibr">82</xref>,<xref rid="R83" ref-type="bibr">83</xref>].</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Mycoplasma</td><td align="left" valign="top" rowspan="1" colspan="1">Presence of DNA [<xref rid="R18" ref-type="bibr">18</xref>,<xref rid="R19" ref-type="bibr">19</xref>] and glycoglycerophospholipids (GGPL) [<xref rid="R29" ref-type="bibr">29</xref>] in RA patients.<break></break>Immune responses to mycoplasma in RA patients [<xref rid="R39" ref-type="bibr">39</xref>,<xref rid="R40" ref-type="bibr">40</xref>].</td><td align="left" valign="top" rowspan="1" colspan="1">Immunization with mycoplasma arthritidis induced or exacerbated arthritis [<xref rid="R46" ref-type="bibr">46</xref>,<xref rid="R50" ref-type="bibr">50</xref>,<xref rid="R84" ref-type="bibr">84</xref>].</td><td align="left" valign="top" rowspan="1" colspan="1">Superantigen [<xref rid="R40" ref-type="bibr">40</xref>,<xref rid="R50" ref-type="bibr">50</xref>].<break></break>Bystander activation [<xref rid="R29" ref-type="bibr">29</xref>].</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/EdenteV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 0007859 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 0007859 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Santé
|area= EdenteV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.33. |  |