Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes
Identifieur interne : 000892 ( Pmc/Checkpoint ); précédent : 000891; suivant : 000893Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes
Auteurs : Ana Clara Monsalvo [Argentine] ; Juan P. Batalle [Argentine] ; M. Florencia Lopez [Argentine] ; Jens C. Krause [États-Unis] ; Jennifer Klemenc [États-Unis] ; Johanna Zea [Argentine, États-Unis] ; Bernardo Maskin [Argentine] ; Jimena Bugna [Argentine] ; Carlos Rubinstein [Argentine] ; Leandro Aguilar [Argentine] ; Liliana Dalurzo [Argentine] ; Romina Libster [Argentine] ; Vilma Savy [Argentine] ; Elsa Baumeister [Argentine] ; Liliana Aguilar [Argentine] ; Graciela Cabral [Argentine] ; Julia Font [Argentine] ; Liliana Solari [Argentine] ; Kevin P. Weller [États-Unis] ; Joyce Johnson [États-Unis] ; Marcela Echavarria [Argentine] ; Kathryn M. Edwards [États-Unis] ; James D. Chappell [États-Unis] ; James E. Crowe [États-Unis] ; John V. Williams [États-Unis] ; Guillermina A. Melendi [Argentine, États-Unis] ; Fernando P. Polack [Argentine, États-Unis]Source :
- Nature medicine [ 1078-8956 ] ; 2010.
Abstract
Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood
Url:
DOI: 10.1038/nm.2262
PubMed: 21131958
PubMed Central: 3034774
Affiliations:
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Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Aguilar, Liliana" sort="Aguilar, Liliana" uniqKey="Aguilar L" first="Liliana" last="Aguilar">Liliana Aguilar</name><affiliation wicri:level="1"><nlm:aff id="A3"> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Cabral, Graciela" sort="Cabral, Graciela" uniqKey="Cabral G" first="Graciela" last="Cabral">Graciela Cabral</name><affiliation wicri:level="1"><nlm:aff id="A3"> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos 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Kevin P" uniqKey="Weller K" first="Kevin P." last="Weller">Kevin P. Weller</name><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Johnson, Joyce" sort="Johnson, Joyce" uniqKey="Johnson J" first="Joyce" last="Johnson">Joyce Johnson</name><affiliation wicri:level="2"><nlm:aff id="A7"> Department of Pathology, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pathology, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Echavarria, Marcela" sort="Echavarria, Marcela" uniqKey="Echavarria M" first="Marcela" last="Echavarria">Marcela Echavarria</name><affiliation wicri:level="1"><nlm:aff id="A8"> Department of Microbiology, CEMIC, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Department of Microbiology, CEMIC, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Edwards, Kathryn M" sort="Edwards, Kathryn M" uniqKey="Edwards K" first="Kathryn M." last="Edwards">Kathryn M. Edwards</name><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Chappell, James D" sort="Chappell, James D" uniqKey="Chappell J" first="James D." last="Chappell">James D. Chappell</name><affiliation wicri:level="2"><nlm:aff id="A7"> Department of Pathology, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pathology, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Crowe, James E" sort="Crowe, James E" uniqKey="Crowe J" first="James E." last="Crowe">James E. Crowe</name><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Williams, John V" sort="Williams, John V" uniqKey="Williams J" first="John V." last="Williams">John V. Williams</name><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Melendi, Guillermina A" sort="Melendi, Guillermina A" uniqKey="Melendi G" first="Guillermina A." last="Melendi">Guillermina A. 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Polack</name><affiliation wicri:level="1"><nlm:aff id="A1"> Fundacion INFANT, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Fundacion INFANT, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21131958</idno><idno type="pmc">3034774</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034774</idno><idno type="RBID">PMC:3034774</idno><idno type="doi">10.1038/nm.2262</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000C68</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C68</idno><idno type="wicri:Area/Pmc/Curation">000C68</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000C68</idno><idno type="wicri:Area/Pmc/Checkpoint">000892</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000892</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes</title><author><name sortKey="Monsalvo, Ana Clara" sort="Monsalvo, Ana Clara" uniqKey="Monsalvo A" first="Ana Clara" last="Monsalvo">Ana Clara Monsalvo</name><affiliation wicri:level="1"><nlm:aff id="A1"> Fundacion INFANT, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Fundacion INFANT, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Batalle, Juan P" sort="Batalle, Juan P" uniqKey="Batalle J" first="Juan P." last="Batalle">Juan P. Batalle</name><affiliation wicri:level="1"><nlm:aff id="A1"> Fundacion INFANT, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Fundacion INFANT, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Lopez, M Florencia" sort="Lopez, M Florencia" uniqKey="Lopez M" first="M. Florencia" last="Lopez">M. Florencia Lopez</name><affiliation wicri:level="1"><nlm:aff id="A1"> Fundacion INFANT, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Fundacion INFANT, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Krause, Jens C" sort="Krause, Jens C" uniqKey="Krause J" first="Jens C." last="Krause">Jens C. Krause</name><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Klemenc, Jennifer" sort="Klemenc, Jennifer" uniqKey="Klemenc J" first="Jennifer" last="Klemenc">Jennifer Klemenc</name><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Zea, Johanna" sort="Zea, Johanna" uniqKey="Zea J" first="Johanna" last="Zea">Johanna Zea</name><affiliation wicri:level="1"><nlm:aff id="A1"> Fundacion INFANT, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Fundacion INFANT, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Maskin, Bernardo" sort="Maskin, Bernardo" uniqKey="Maskin B" first="Bernardo" last="Maskin">Bernardo Maskin</name><affiliation wicri:level="1"><nlm:aff id="A3"> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Bugna, Jimena" sort="Bugna, Jimena" uniqKey="Bugna J" first="Jimena" last="Bugna">Jimena Bugna</name><affiliation wicri:level="1"><nlm:aff id="A1"> Fundacion INFANT, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Fundacion INFANT, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Rubinstein, Carlos" sort="Rubinstein, Carlos" uniqKey="Rubinstein C" first="Carlos" last="Rubinstein">Carlos Rubinstein</name><affiliation wicri:level="1"><nlm:aff id="A4"> Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Aguilar, Leandro" sort="Aguilar, Leandro" uniqKey="Aguilar L" first="Leandro" last="Aguilar">Leandro Aguilar</name><affiliation wicri:level="1"><nlm:aff id="A4"> Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Dalurzo, Liliana" sort="Dalurzo, Liliana" uniqKey="Dalurzo L" first="Liliana" last="Dalurzo">Liliana Dalurzo</name><affiliation wicri:level="1"><nlm:aff id="A5"> Hospital Italiano, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Hospital Italiano, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Libster, Romina" sort="Libster, Romina" uniqKey="Libster R" first="Romina" last="Libster">Romina Libster</name><affiliation wicri:level="1"><nlm:aff id="A1"> Fundacion INFANT, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Fundacion INFANT, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Savy, Vilma" sort="Savy, Vilma" uniqKey="Savy V" first="Vilma" last="Savy">Vilma Savy</name><affiliation wicri:level="1"><nlm:aff id="A6"> ANLIS Dr Carlos G Malbran, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> ANLIS Dr Carlos G Malbran, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Baumeister, Elsa" sort="Baumeister, Elsa" uniqKey="Baumeister E" first="Elsa" last="Baumeister">Elsa Baumeister</name><affiliation wicri:level="1"><nlm:aff id="A6"> ANLIS Dr Carlos G Malbran, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> ANLIS Dr Carlos G Malbran, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Aguilar, Liliana" sort="Aguilar, Liliana" uniqKey="Aguilar L" first="Liliana" last="Aguilar">Liliana Aguilar</name><affiliation wicri:level="1"><nlm:aff id="A3"> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Cabral, Graciela" sort="Cabral, Graciela" uniqKey="Cabral G" first="Graciela" last="Cabral">Graciela Cabral</name><affiliation wicri:level="1"><nlm:aff id="A3"> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Font, Julia" sort="Font, Julia" uniqKey="Font J" first="Julia" last="Font">Julia Font</name><affiliation wicri:level="1"><nlm:aff id="A3"> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Solari, Liliana" sort="Solari, Liliana" uniqKey="Solari L" first="Liliana" last="Solari">Liliana Solari</name><affiliation wicri:level="1"><nlm:aff id="A3"> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Weller, Kevin P" sort="Weller, Kevin P" uniqKey="Weller K" first="Kevin P." last="Weller">Kevin P. Weller</name><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Johnson, Joyce" sort="Johnson, Joyce" uniqKey="Johnson J" first="Joyce" last="Johnson">Joyce Johnson</name><affiliation wicri:level="2"><nlm:aff id="A7"> Department of Pathology, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pathology, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Echavarria, Marcela" sort="Echavarria, Marcela" uniqKey="Echavarria M" first="Marcela" last="Echavarria">Marcela Echavarria</name><affiliation wicri:level="1"><nlm:aff id="A8"> Department of Microbiology, CEMIC, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Department of Microbiology, CEMIC, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Edwards, Kathryn M" sort="Edwards, Kathryn M" uniqKey="Edwards K" first="Kathryn M." last="Edwards">Kathryn M. Edwards</name><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Chappell, James D" sort="Chappell, James D" uniqKey="Chappell J" first="James D." last="Chappell">James D. Chappell</name><affiliation wicri:level="2"><nlm:aff id="A7"> Department of Pathology, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pathology, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Crowe, James E" sort="Crowe, James E" uniqKey="Crowe J" first="James E." last="Crowe">James E. Crowe</name><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Williams, John V" sort="Williams, John V" uniqKey="Williams J" first="John V." last="Williams">John V. Williams</name><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Melendi, Guillermina A" sort="Melendi, Guillermina A" uniqKey="Melendi G" first="Guillermina A." last="Melendi">Guillermina A. Melendi</name><affiliation wicri:level="1"><nlm:aff id="A1"> Fundacion INFANT, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Fundacion INFANT, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author><author><name sortKey="Polack, Fernando P" sort="Polack, Fernando P" uniqKey="Polack F" first="Fernando P." last="Polack">Fernando P. Polack</name><affiliation wicri:level="1"><nlm:aff id="A1"> Fundacion INFANT, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea> Fundacion INFANT, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:aff id="A2"> Department of Pediatrics, Vanderbilt University, Nashville, TN</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea> Department of Pediatrics, Vanderbilt University, Nashville</wicri:cityArea></affiliation></author></analytic><series><title level="j">Nature medicine</title><idno type="ISSN">1078-8956</idno><idno type="eISSN">1546-170X</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood<xref rid="R1" ref-type="bibr">1</xref>–<xref rid="R10" ref-type="bibr">10</xref>. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Morens, Dm" uniqKey="Morens D">DM Morens</name></author><author><name sortKey="Taubenberger, Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author><author><name sortKey="Fauci, As" uniqKey="Fauci A">AS Fauci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tumpey, Tm" uniqKey="Tumpey T">TM Tumpey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Itoh, Y" uniqKey="Itoh Y">Y Itoh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kobasa, D" uniqKey="Kobasa D">D Kobasa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Geiss, Gk" uniqKey="Geiss G">GK 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<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9502015</journal-id><journal-id journal-id-type="pubmed-jr-id">8791</journal-id><journal-id journal-id-type="nlm-ta">Nat Med</journal-id><journal-id journal-id-type="iso-abbrev">Nat. Med.</journal-id><journal-title-group><journal-title>Nature medicine</journal-title></journal-title-group><issn pub-type="ppub">1078-8956</issn><issn pub-type="epub">1546-170X</issn></journal-meta><article-meta><article-id pub-id-type="pmid">21131958</article-id><article-id pub-id-type="pmc">3034774</article-id><article-id pub-id-type="doi">10.1038/nm.2262</article-id><article-id pub-id-type="manuscript">NIHMS247007</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Monsalvo</surname><given-names>Ana Clara</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Batalle</surname><given-names>Juan P.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Lopez</surname><given-names>M. Florencia</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Krause</surname><given-names>Jens C.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Klemenc</surname><given-names>Jennifer</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Zea</surname><given-names>Johanna</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>Maskin</surname><given-names>Bernardo</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Bugna</surname><given-names>Jimena</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Rubinstein</surname><given-names>Carlos</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Aguilar</surname><given-names>Leandro</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Dalurzo</surname><given-names>Liliana</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Libster</surname><given-names>Romina</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Savy</surname><given-names>Vilma</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Baumeister</surname><given-names>Elsa</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Aguilar</surname><given-names>Liliana</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cabral</surname><given-names>Graciela</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Font</surname><given-names>Julia</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Solari</surname><given-names>Liliana</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Weller</surname><given-names>Kevin P.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Johnson</surname><given-names>Joyce</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Echavarria</surname><given-names>Marcela</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Edwards</surname><given-names>Kathryn M.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Chappell</surname><given-names>James D.</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Crowe</surname><given-names>James E.</given-names><suffix>Jr.</suffix></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Williams</surname><given-names>John V.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Melendi</surname><given-names>Guillermina A.</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>Polack</surname><given-names>Fernando P.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib></contrib-group><aff id="A1"><label>1</label> Fundacion INFANT, Buenos Aires, Argentina</aff><aff id="A2"><label>2</label> Department of Pediatrics, Vanderbilt University, Nashville, TN</aff><aff id="A3"><label>3</label> Hospital Nacional Prof. Alejandro Posadas, Buenos Aires, Argentina</aff><aff id="A4"><label>4</label> Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires, Argentina</aff><aff id="A5"><label>5</label> Hospital Italiano, Buenos Aires, Argentina</aff><aff id="A6"><label>6</label> ANLIS Dr Carlos G Malbran, Buenos Aires, Argentina</aff><aff id="A7"><label>7</label> Department of Pathology, Vanderbilt University, Nashville, TN</aff><aff id="A8"><label>8</label> Department of Microbiology, CEMIC, Buenos Aires, Argentina</aff><author-notes><corresp id="FN1">Corresponding authors: Fernando P. Polack, MD; Department of Pediatrics; Vanderbilt University; <email>fernando.p.polack@vanderbilt.edu</email> and Guillermina A. Melendi; Fundacion INFANT; Buenos Aires, Argentina; <email>gmelendi@infant.org.ar</email></corresp><fn id="FN2" fn-type="equal"><label>*</label><p>MFL, ACM and JPB contributed equally to this manuscript.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>9</day><month>11</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>05</day><month>12</month><year>2010</year></pub-date><pub-date pub-type="ppub"><month>2</month><year>2011</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>8</month><year>2011</year></pub-date><volume>17</volume><issue>2</issue><fpage>195</fpage><lpage>199</lpage><pmc-comment>elocation-id from pubmed: 10.1038/nm.2262</pmc-comment>
<permissions><license><license-p>Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: <ext-link ext-link-type="uri" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</ext-link></license-p></license></permissions><abstract><p id="P1">Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood<xref rid="R1" ref-type="bibr">1</xref>–<xref rid="R10" ref-type="bibr">10</xref>. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics.</p></abstract></article-meta></front><floats-group><fig id="F1" position="float"><label>Figure 1</label><caption><title>Histopathology and virus titers in 2009 H1N1 disease</title><p>(a) Pulmonary histopathology in representative lung sections of fatal 2009 H1N1 and seasonal H1N1 virus infected patients (H&E). (b) Detection of 2009 H1N1 and seasonal H1N1 influenza viruses. Scale, 100μm. The boxes are details of pulmonary edema (2009 H1N1, H&E), peribronchiolar mononuclear cell infiltration (seasonal H1N1, H&E), and virus-infected cells (anti-H1N1 stains). (c) 2009 H1N1 RT-PCR C(t) values in NP secretions of fatal (black circles), ICU (black squares) and ambulatory (black triangles) patients; p=NS. (d) 2009 H1N1 RT-PCR C(t) values by days of symptoms before NP sampling.</p></caption><graphic xlink:href="nihms247007f1"></graphic></fig><fig id="F2" position="float"><label>Figure 2</label><caption><title>Inflammation in influenza A 2009 H1N1 disease</title><p>IL-8(a), TNF-α (b), IL-6(c) and IL-1β (d) responses in respiratory secretions of patients infected with 2009 H1N1 influenza virus (tracheal aspirates, white circles; NP secretions, black squares) or seasonal influenza viruses (NP secretions of: H1N1, black up-pointing triangles; H3N2, black down-pointing triangles). Comparisons for NP secretions: IL-8, p=0.01; all other cytokines, p=NS. IL-1β (e), IL-6(f), IL-10 (g), and TNF-α (h) production by human monocytes incubated with a dose range of recombinant protein H1-1918 (black squares), H1-1999 (black triangles), H1-2009 (black circles), avian H5 (gray circles), hMPV F (white circles), and a control monoclonal human IgG against the Sa antigenic site of influenza HA (2D1; black diamond). Representative of three independent experiments. (i) Individual TLR activation in HEK293 cells. Dose: 5μg of H1-1918 (white bars), H1-1999 (yellow bars), H1-2009 (green bars), hMPV F (blue bars), and no ligand (red bars). Representative of two independent experiments.</p></caption><graphic xlink:href="nihms247007f2"></graphic></fig><fig id="F3" position="float"><label>Figure 3</label><caption><title>Lymphopenia in influenza A 2009 H1N1 disease</title><p>(a)CD3<sup>+</sup>, (b) CD4<sup>+</sup> and (c) CD8<sup>+</sup> T lymphocyte counts in fatal and ICU patients infected with 2009 H1N1 influenza A virus on admission. Immunohistochemistry for (d)CD3<sup>+</sup> T lymphocytes (red arrows), (e)CD8<sup>+</sup> T lymphocytes(yellow arrows) in representative lung sections of fatal influenza 2009 H1N1 and seasonal infection. Positive controls are archived sections from different organs in unrelated subjects provided for every antibody. Negative controls are lung sections from a patient who died due to a non-pulmonary disease (scale, 100μm).</p></caption><graphic xlink:href="nihms247007f3"></graphic></fig><fig id="F4" position="float"><label>Figure 4</label><caption><title>IC-mediated disease in 2009 H1N1 influenza infection</title><p>(a) Serum IgG endpoint titers against HA proteins by immunoassay in infants [mean age(range)=7.6 mo(6.1–11.8); n=10; white bars], middle-aged adults (n=16; gray bars), and elderly (n=12; black bars). (b) Protein-specific avidity of IgG after 6–9M urea wash in naïve adults (age range=25–43 year old; black squares) and elderly (age range= 75–97 years old; black diamonds); p<0.05. (c) Microneutralization titers for infants (black circles), adults (black squares) and elderly (black triangles); p value for elderly vs. both groups <0.05. (d) End point titer of serum IgG against H1-2009 antigens by immunoassay in adults with severe (n=12) vs mild (n=11) disease, p<0.05. (e) H1-2009-specific avidity of IgG after 7–9M urea wash in infected adults with severe (n=12) vs. mild (n=11) pandemic disease, p<0.05. (f) H1-2009-specific avidity of IgG from immune complexes after 8M urea wash in infected adults with severe (n=14) vs. mild (n=11) pandemic disease, p<0.05. (g) C4d detection in representative slides from lung sections of 2 of 6 fatal 2009 H1N1 infected middle-aged patients showing extensive peribronchiolar IC-mediated complement activation. Trace C4d deposition in representative lung section of fatal seasonal H1N1 virus from an elderly woman. Positive control: C4d deposition in a kidney from an adult patient with IC-mediated glomerulonephritis; negative control: lung section from an adult patient with solid tumor (scale, 100 μm). (h) Serum complement C3 levels in ICU adults (white circles), floor adults(black squares) and in infants (black circles) infected with H1N1 2009 influenza A virus, adults infected with seasonal influenza virus (black triangles) and adult patients with pulmonary diseases other than influenza in ICU and floor (white diamonds); p=0.036 (i) C4d detection in representative slides from lung sections of two fatal 1957 H2N2 influenza-infected patients showing extensive peribronchiolar deposition of complement cleavage product. Negative control from an archived sample with no infectious pulmonary disease. The box in the microphotograph is a detail of lung complement deposition.</p></caption><graphic xlink:href="nihms247007f4"></graphic></fig></floats-group></pmc><affiliations><list><country><li>Argentine</li><li>États-Unis</li></country><region><li>Tennessee</li></region></list><tree><country name="Argentine"><noRegion><name sortKey="Monsalvo, Ana Clara" sort="Monsalvo, Ana Clara" uniqKey="Monsalvo A" first="Ana Clara" last="Monsalvo">Ana Clara Monsalvo</name></noRegion><name sortKey="Aguilar, Leandro" sort="Aguilar, Leandro" uniqKey="Aguilar L" first="Leandro" last="Aguilar">Leandro Aguilar</name><name sortKey="Aguilar, Liliana" sort="Aguilar, Liliana" uniqKey="Aguilar L" first="Liliana" last="Aguilar">Liliana Aguilar</name><name sortKey="Batalle, Juan P" sort="Batalle, Juan P" uniqKey="Batalle J" first="Juan P." last="Batalle">Juan P. Batalle</name><name sortKey="Baumeister, Elsa" sort="Baumeister, Elsa" uniqKey="Baumeister E" first="Elsa" last="Baumeister">Elsa Baumeister</name><name sortKey="Bugna, Jimena" sort="Bugna, Jimena" uniqKey="Bugna J" first="Jimena" last="Bugna">Jimena Bugna</name><name sortKey="Cabral, Graciela" sort="Cabral, Graciela" uniqKey="Cabral G" first="Graciela" last="Cabral">Graciela Cabral</name><name sortKey="Dalurzo, Liliana" sort="Dalurzo, Liliana" uniqKey="Dalurzo L" first="Liliana" last="Dalurzo">Liliana Dalurzo</name><name sortKey="Echavarria, Marcela" sort="Echavarria, Marcela" uniqKey="Echavarria M" first="Marcela" last="Echavarria">Marcela Echavarria</name><name sortKey="Font, Julia" sort="Font, Julia" uniqKey="Font J" first="Julia" last="Font">Julia Font</name><name sortKey="Libster, Romina" sort="Libster, Romina" uniqKey="Libster R" first="Romina" last="Libster">Romina Libster</name><name sortKey="Lopez, M Florencia" sort="Lopez, M Florencia" uniqKey="Lopez M" first="M. Florencia" last="Lopez">M. Florencia Lopez</name><name sortKey="Maskin, Bernardo" sort="Maskin, Bernardo" uniqKey="Maskin B" first="Bernardo" last="Maskin">Bernardo Maskin</name><name sortKey="Melendi, Guillermina A" sort="Melendi, Guillermina A" uniqKey="Melendi G" first="Guillermina A." last="Melendi">Guillermina A. Melendi</name><name sortKey="Polack, Fernando P" sort="Polack, Fernando P" uniqKey="Polack F" first="Fernando P." last="Polack">Fernando P. Polack</name><name sortKey="Rubinstein, Carlos" sort="Rubinstein, Carlos" uniqKey="Rubinstein C" first="Carlos" last="Rubinstein">Carlos Rubinstein</name><name sortKey="Savy, Vilma" sort="Savy, Vilma" uniqKey="Savy V" first="Vilma" last="Savy">Vilma Savy</name><name sortKey="Solari, Liliana" sort="Solari, Liliana" uniqKey="Solari L" first="Liliana" last="Solari">Liliana Solari</name><name sortKey="Zea, Johanna" sort="Zea, Johanna" uniqKey="Zea J" first="Johanna" last="Zea">Johanna Zea</name></country><country name="États-Unis"><region name="Tennessee"><name sortKey="Krause, Jens C" sort="Krause, Jens C" uniqKey="Krause J" first="Jens C." last="Krause">Jens C. Krause</name></region><name sortKey="Chappell, James D" sort="Chappell, James D" uniqKey="Chappell J" first="James D." last="Chappell">James D. Chappell</name><name sortKey="Crowe, James E" sort="Crowe, James E" uniqKey="Crowe J" first="James E." last="Crowe">James E. Crowe</name><name sortKey="Edwards, Kathryn M" sort="Edwards, Kathryn M" uniqKey="Edwards K" first="Kathryn M." last="Edwards">Kathryn M. Edwards</name><name sortKey="Johnson, Joyce" sort="Johnson, Joyce" uniqKey="Johnson J" first="Joyce" last="Johnson">Joyce Johnson</name><name sortKey="Klemenc, Jennifer" sort="Klemenc, Jennifer" uniqKey="Klemenc J" first="Jennifer" last="Klemenc">Jennifer Klemenc</name><name sortKey="Melendi, Guillermina A" sort="Melendi, Guillermina A" uniqKey="Melendi G" first="Guillermina A." last="Melendi">Guillermina A. Melendi</name><name sortKey="Polack, Fernando P" sort="Polack, Fernando P" uniqKey="Polack F" first="Fernando P." last="Polack">Fernando P. Polack</name><name sortKey="Weller, Kevin P" sort="Weller, Kevin P" uniqKey="Weller K" first="Kevin P." last="Weller">Kevin P. Weller</name><name sortKey="Williams, John V" sort="Williams, John V" uniqKey="Williams J" first="John V." last="Williams">John V. Williams</name><name sortKey="Zea, Johanna" sort="Zea, Johanna" uniqKey="Zea J" first="Johanna" last="Zea">Johanna Zea</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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