Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection
Identifieur interne : 000040 ( Pmc/Corpus ); précédent : 000039; suivant : 000041Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection
Auteurs : Ali H. Hajeer ; Hanan Balkhy ; Sameera Johani ; Mohammed Z. Yousef ; Yaseen ArabiSource :
- Annals of Thoracic Medicine [ 1817-1737 ] ; 2016.
Abstract
Middle East Respiratory Syndrome (MERS) is a disease of the lower respiratory tract and is characterized by high mortality. It is caused by a beta coronavirus (CoV) referred to as MERS-CoV. Majority of MERS-CoV cases have been reported from Saudi Arabia.
We investigated the human leukocyte antigen (HLA) Class II alleles in patients with severe MERS who were admitted in our Intensive Care Unit.
A total of 23 Saudi patients with severe MERS-CoV infection were typed for HLA class II, results were compared with those of 161 healthy controls.
Two HLA class II alleles were associated with the disease; HLA-DRB1*11:01 and DQB1*02:02, but not with the disease outcome.
Our results suggest that the HLA-DRB1*11:01 and DQB1*02:02 may be associated with susceptibility to MERS.
Url:
DOI: 10.4103/1817-1737.185756
PubMed: 27512511
PubMed Central: 4966224
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection</title><author><name sortKey="Hajeer, Ali H" sort="Hajeer, Ali H" uniqKey="Hajeer A" first="Ali H." last="Hajeer">Ali H. Hajeer</name><affiliation><nlm:aff id="aff1"><italic>Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><italic>Department of Pathology and Laboratory, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation></author><author><name sortKey="Balkhy, Hanan" sort="Balkhy, Hanan" uniqKey="Balkhy H" first="Hanan" last="Balkhy">Hanan Balkhy</name><affiliation><nlm:aff id="aff3"><italic>Department of Infection Prevention and Control, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><italic>King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation></author><author><name sortKey="Johani, Sameera" sort="Johani, Sameera" uniqKey="Johani S" first="Sameera" last="Johani">Sameera Johani</name><affiliation><nlm:aff id="aff2"><italic>Department of Pathology and Laboratory, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation></author><author><name sortKey="Yousef, Mohammed Z" sort="Yousef, Mohammed Z" uniqKey="Yousef M" first="Mohammed Z." last="Yousef">Mohammed Z. Yousef</name><affiliation><nlm:aff id="aff1"><italic>Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation></author><author><name sortKey="Arabi, Yaseen" sort="Arabi, Yaseen" uniqKey="Arabi Y" first="Yaseen" last="Arabi">Yaseen Arabi</name><affiliation><nlm:aff id="aff4"><italic>King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"><italic>Department of Intensive Care, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27512511</idno><idno type="pmc">4966224</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966224</idno><idno type="RBID">PMC:4966224</idno><idno type="doi">10.4103/1817-1737.185756</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000040</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000040</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection</title><author><name sortKey="Hajeer, Ali H" sort="Hajeer, Ali H" uniqKey="Hajeer A" first="Ali H." last="Hajeer">Ali H. Hajeer</name><affiliation><nlm:aff id="aff1"><italic>Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><italic>Department of Pathology and Laboratory, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation></author><author><name sortKey="Balkhy, Hanan" sort="Balkhy, Hanan" uniqKey="Balkhy H" first="Hanan" last="Balkhy">Hanan Balkhy</name><affiliation><nlm:aff id="aff3"><italic>Department of Infection Prevention and Control, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><italic>King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation></author><author><name sortKey="Johani, Sameera" sort="Johani, Sameera" uniqKey="Johani S" first="Sameera" last="Johani">Sameera Johani</name><affiliation><nlm:aff id="aff2"><italic>Department of Pathology and Laboratory, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation></author><author><name sortKey="Yousef, Mohammed Z" sort="Yousef, Mohammed Z" uniqKey="Yousef M" first="Mohammed Z." last="Yousef">Mohammed Z. Yousef</name><affiliation><nlm:aff id="aff1"><italic>Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation></author><author><name sortKey="Arabi, Yaseen" sort="Arabi, Yaseen" uniqKey="Arabi Y" first="Yaseen" last="Arabi">Yaseen Arabi</name><affiliation><nlm:aff id="aff4"><italic>King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"><italic>Department of Intensive Care, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></nlm:aff></affiliation></author></analytic><series><title level="j">Annals of Thoracic Medicine</title><idno type="ISSN">1817-1737</idno><idno type="eISSN">1998-3557</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="st1"><title>BACKGROUND:</title><p>Middle East Respiratory Syndrome (MERS) is a disease of the lower respiratory tract and is characterized by high mortality. It is caused by a beta coronavirus (CoV) referred to as MERS-CoV. Majority of MERS-CoV cases have been reported from Saudi Arabia.</p></sec><sec id="st2"><title>AIM:</title><p>We investigated the human leukocyte antigen (HLA) Class II alleles in patients with severe MERS who were admitted in our Intensive Care Unit.</p></sec><sec id="st3"><title>METHODS:</title><p>A total of 23 Saudi patients with severe MERS-CoV infection were typed for HLA class II, results were compared with those of 161 healthy controls.</p></sec><sec id="st4"><title>RESULTS:</title><p>Two HLA class II alleles were associated with the disease; HLA-DRB1*11:01 and DQB1*02:02, but not with the disease outcome.</p></sec><sec id="st5"><title>CONCLUSIONS:</title><p>Our results suggest that the HLA-DRB1*11:01 and DQB1*02:02 may be associated with susceptibility to MERS.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Arifi, Aa" uniqKey="Arifi A">AA Arifi</name></author><author><name sortKey="Balkhy, Hh" uniqKey="Balkhy H">HH Balkhy</name></author><author><name sortKey="Najm, H" uniqKey="Najm H">H Najm</name></author><author><name sortKey="Aldawood, As" uniqKey="Aldawood A">AS Aldawood</name></author><author><name sortKey="Ghabashi, A" uniqKey="Ghabashi A">A Ghabashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klein, J" uniqKey="Klein J">J Klein</name></author><author><name sortKey="Sato, A" uniqKey="Sato A">A Sato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xiong, P" uniqKey="Xiong P">P Xiong</name></author><author><name sortKey="Zeng, X" uniqKey="Zeng X">X Zeng</name></author><author><name sortKey="Song, Ms" uniqKey="Song M">MS Song</name></author><author><name sortKey="Jia, Sw" uniqKey="Jia S">SW Jia</name></author><author><name sortKey="Zhong, Mh" uniqKey="Zhong M">MH Zhong</name></author><author><name sortKey="Xiao, Ll" uniqKey="Xiao L">LL Xiao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, M" uniqKey="Lin M">M Lin</name></author><author><name sortKey="Tseng, Hk" uniqKey="Tseng H">HK Tseng</name></author><author><name sortKey="Trejaut, Ja" uniqKey="Trejaut J">JA Trejaut</name></author><author><name sortKey="Lee, Hl" uniqKey="Lee H">HL Lee</name></author><author><name sortKey="Loo, Jh" uniqKey="Loo J">JH Loo</name></author><author><name sortKey="Chu, Cc" uniqKey="Chu C">CC Chu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chastel, C" uniqKey="Chastel C">C Chastel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hajeer, Ah" uniqKey="Hajeer A">AH Hajeer</name></author><author><name sortKey="Al Balwi, Ma" uniqKey="Al Balwi M">MA Al Balwi</name></author><author><name sortKey="Aytul Uyar, F" uniqKey="Aytul Uyar F">F Aytül Uyar</name></author><author><name sortKey="Alhaidan, Y" uniqKey="Alhaidan Y">Y Alhaidan</name></author><author><name sortKey="Alabdulrahman, A" uniqKey="Alabdulrahman A">A Alabdulrahman</name></author><author><name sortKey="Al Abdulkareem, I" uniqKey="Al Abdulkareem I">I Al Abdulkareem</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="In, Jw" uniqKey="In J">JW In</name></author><author><name sortKey="Roh, Ey" uniqKey="Roh E">EY Roh</name></author><author><name sortKey="Oh, S" uniqKey="Oh S">S Oh</name></author><author><name sortKey="Shin, S" uniqKey="Shin S">S Shin</name></author><author><name sortKey="Park, Ku" uniqKey="Park K">KU Park</name></author><author><name sortKey="Song, Ey" uniqKey="Song E">EY Song</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cowling, Bj" uniqKey="Cowling B">BJ Cowling</name></author><author><name sortKey="Park, M" uniqKey="Park M">M Park</name></author><author><name sortKey="Fang, Vj" uniqKey="Fang V">VJ Fang</name></author><author><name sortKey="Wu, P" uniqKey="Wu P">P Wu</name></author><author><name sortKey="Leung, Gm" uniqKey="Leung G">GM Leung</name></author><author><name sortKey="Wu, Jt" uniqKey="Wu J">JT Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ng, Mh" uniqKey="Ng M">MH Ng</name></author><author><name sortKey="Cheng, Sh" uniqKey="Cheng S">SH Cheng</name></author><author><name sortKey="Lau, Km" uniqKey="Lau K">KM Lau</name></author><author><name sortKey="Leung, Gm" uniqKey="Leung G">GM Leung</name></author><author><name sortKey="Khoo, Us" uniqKey="Khoo U">US Khoo</name></author><author><name sortKey="Zee, Bc" uniqKey="Zee B">BC Zee</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Ann Thorac Med</journal-id><journal-id journal-id-type="iso-abbrev">Ann Thorac Med</journal-id><journal-id journal-id-type="publisher-id">ATM</journal-id><journal-title-group><journal-title>Annals of Thoracic Medicine</journal-title></journal-title-group><issn pub-type="ppub">1817-1737</issn><issn pub-type="epub">1998-3557</issn><publisher><publisher-name>Medknow Publications & Media Pvt Ltd</publisher-name><publisher-loc>India</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27512511</article-id><article-id pub-id-type="pmc">4966224</article-id><article-id pub-id-type="publisher-id">ATM-11-211</article-id><article-id pub-id-type="doi">10.4103/1817-1737.185756</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Hajeer</surname><given-names>Ali H.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="corresp" rid="cor1"></xref></contrib><contrib contrib-type="author"><name><surname>Balkhy</surname><given-names>Hanan</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Johani</surname><given-names>Sameera</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Yousef</surname><given-names>Mohammed Z.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Arabi</surname><given-names>Yaseen</given-names></name><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib></contrib-group><aff id="aff1"><label>1</label><italic>Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></aff><aff id="aff2"><label>2</label><italic>Department of Pathology and Laboratory, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></aff><aff id="aff3"><label>3</label><italic>Department of Infection Prevention and Control, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></aff><aff id="aff4"><label>4</label><italic>King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></aff><aff id="aff5"><label>5</label><italic>Department of Intensive Care, King Abdulaziz Medical City, Riyadh, Saudi Arabia</italic></aff><author-notes><corresp id="cor1"><bold>Address for correspondence:</bold> Dr. Ali H. Hajeer, Department of Basic Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, P. O. Box: 3660 Riyadh 11481, Saudi Arabia. E-mail: <email xlink:href="hajeera@ksau-hs.edu.sa">hajeera@ksau-hs.edu.sa</email></corresp></author-notes><pub-date pub-type="ppub"><season>Jul-Sep</season><year>2016</year></pub-date><volume>11</volume><issue>3</issue><fpage>211</fpage><lpage>213</lpage><history><date date-type="received"><day>14</day><month>4</month><year>2016</year></date><date date-type="accepted"><day>01</day><month>5</month><year>2016</year></date></history><permissions><copyright-statement>Copyright: © <italic>2016 Annals of</italic> Thoracic Medicine</copyright-statement><copyright-year>2016</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.</license-p></license></permissions><abstract><sec id="st1"><title>BACKGROUND:</title><p>Middle East Respiratory Syndrome (MERS) is a disease of the lower respiratory tract and is characterized by high mortality. It is caused by a beta coronavirus (CoV) referred to as MERS-CoV. Majority of MERS-CoV cases have been reported from Saudi Arabia.</p></sec><sec id="st2"><title>AIM:</title><p>We investigated the human leukocyte antigen (HLA) Class II alleles in patients with severe MERS who were admitted in our Intensive Care Unit.</p></sec><sec id="st3"><title>METHODS:</title><p>A total of 23 Saudi patients with severe MERS-CoV infection were typed for HLA class II, results were compared with those of 161 healthy controls.</p></sec><sec id="st4"><title>RESULTS:</title><p>Two HLA class II alleles were associated with the disease; HLA-DRB1*11:01 and DQB1*02:02, but not with the disease outcome.</p></sec><sec id="st5"><title>CONCLUSIONS:</title><p>Our results suggest that the HLA-DRB1*11:01 and DQB1*02:02 may be associated with susceptibility to MERS.</p></sec></abstract><kwd-group><kwd>Human leukocyte Antigen Class II</kwd><kwd>Middle East respiratory syndrome-coronavirus</kwd><kwd>Saudi Arabia</kwd></kwd-group></article-meta></front><body><p>Middle East respiratory syndrome (MERS) is caused by a novel coronavirus (MERS-CoV).[<xref rid="ref1" ref-type="bibr">1</xref>] In Saudi Arabia, Zaki <italic>et al</italic>. reported the first case of MERS presenting with acute pneumonia that subsequently lead to renal failure and fatal outcome.[<xref rid="ref1" ref-type="bibr">1</xref>] This was followed by multiple outbreaks although so far the majority of the reported cases are from Saudi Arabia.[<xref rid="ref2" ref-type="bibr">2</xref>] MERS presents as acute respiratory syndrome, but majority of cases suffer from shock, acute kidney injury, and thrombocytopenia which lead to high morbidity.[<xref rid="ref3" ref-type="bibr">3</xref>] It is unclear whether the clustering of cases in Saudi Arabia is related to host genetic predisposition such as the human leukocyte antigen (HLA).</p><p>HLA Class I and II genes encode protein receptors that orchestrate the immune response by presenting foreign or modified self-antigens to T-cells.[<xref rid="ref4" ref-type="bibr">4</xref>] MERS-CoV is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV). Studies on the HLA associations in SARS showed conflicting results. Xiong <italic>et al</italic>. showed no HLA allele association in 95 Chinese SARS patients,[<xref rid="ref5" ref-type="bibr">5</xref>] whereas Lin <italic>et al</italic>. showed that severe SARS was associated with HLA-B*46:01 in Taiwanese patients.[<xref rid="ref6" ref-type="bibr">6</xref>]</p><p>To date, it remains unclear why most cases have been reported in Saudi Arabia although evidence for infection among camels have been demonstrated in a much geographically dispersed area including East Africa and Spain.[<xref rid="ref7" ref-type="bibr">7</xref>] In addition, it remains unclear why some patients develop severe MERS-CoV illness with high mortality.</p><p>In this study, we recruited MERS patients admitted to Intensive Care Unit (ICU) at King Abdulaziz Medical City to study the association between HLA Class II alleles and severe MERS disease.</p><sec sec-type="methods" id="sec1-1"><title>Methods</title><p>This study comprised 23 consecutive Saudi MERS patients admitted to ICU at King Abdulaziz Medical City, Riyadh. All patients confirmed to have laboratory-confirmed MERS-CoV infection by real-time reverse transcription-polymerase chain reaction of nasopharyngeal swabs or tracheal aspirates (TIB Molbiol GMbH, Berlin, Germany). The study was approved by the local Institutional Review Board Committee and written informed consent was obtained from the patient or next of kin.</p><sec id="sec2-1"><title>Control group</title><p>A group of 161 healthy individuals were available for comparison. All were Saudi with a mean age of 36 years and almost equal distribution of male and female gender.</p></sec><sec id="sec2-2"><title>Human leukocyte antigen-typing</title><p>HLA typing was carried out using high definition kits LABType<sup>®</sup> SSO HD (One Lambda Inc., Canoga Park, CA, USA). The HLA typing was carried out according to the manufacturers’ instructions. Briefly, the HLA typing procedure comprised DNA extraction, amplification, hybridization, reading on a Luminex machine (LABScan™ 100, One Lambda, Canoga Park, CA, USA), and interpretation was carried out using HLA Fusion™ software (One Lambda, Canoga Park, CA, USA).</p></sec><sec id="sec2-3"><title>Statistical analysis</title><p>Statistical analysis was carried out using STATA 12.0 software (Stata Corporation, College Station, TX, USA). Differences in the HLA-DRB1 and HLA-DQB1 allele frequencies between two groups were compared using Fisher's exact test separately for all alleles and <italic>P</italic> < 0.05 was considered to be statistically significant, after Bonferroni correction for multiple testing. Odds ratio (OR) and 95% confidence interval (CI) were calculated using 2 × 2 tables.</p></sec></sec><sec sec-type="results" id="sec1-2"><title>Results</title><p>As can be seen from <xref ref-type="table" rid="T1">Table 1</xref>, most patients were male and old with very high mortality. The comparison of HLA-DRB1 results between cases and controls revealed one association. HLA-DRB1*11:01 carried a significant association with severe MERS in this Saudi cohort (OR = 6.11, 95% CI 1.36-24.76, <italic>P</italic> = 0.0016, <italic>P</italic> c = 0.022) [<xref ref-type="table" rid="T2">Table 2</xref>]. HLA-DRB1*04:03, 04:05, and 13:02 alleles were overrepresented in the MERS cases but did not reach statistical significance. <xref ref-type="table" rid="T3">Table 3</xref> demonstrates the comparison between the cases and controls for the HLA-DQB1 alleles. HLA-DQB1*02:02 showed positive association with severe MERS infection (OR = 2.64, 95% CI 0.99-7.10, <italic>P</italic> = 0.027, <italic>P</italic> c = 0.27) but this association did not reach significance after correcting for multiple allele testing [<xref ref-type="table" rid="T3">Table 3</xref>]. HLA-DQB1*02:01, 05:01, and 05:02 allele frequencies were reduced in the cases compared to controls but did not reach statistical significance, whereas HLA-DQB1*03:01, 03:02, 06:02, and 06:04 were raised in the cases compared to controls but again did not reach statistical significance [<xref ref-type="table" rid="T3">Table 3</xref>].</p><table-wrap id="T1" position="float"><label>Table 1</label><caption><p>Demographic characteristics of Middle East respiratory syndrome patients</p></caption><graphic xlink:href="ATM-11-211-g001"></graphic></table-wrap><table-wrap id="T2" position="float"><label>Table 2</label><caption><p>Distribution of HLA-DRB1 alleles in Middle East respiratory syndrome-coronavirus patients and controls*</p></caption><graphic xlink:href="ATM-11-211-g002"></graphic></table-wrap><table-wrap id="T3" position="float"><label>Table 3</label><caption><p>Distribution of HLA-DQB1 alleles in Middle East respiratory syndrome-coronavirus patients and controls*</p></caption><graphic xlink:href="ATM-11-211-g003"></graphic></table-wrap></sec><sec sec-type="discussion" id="sec1-3"><title>Discussion</title><p>Until today, the vast majority of MERS-CoV cases came from Saudi Arabia.[<xref rid="ref2" ref-type="bibr">2</xref>] The disease is so severe affecting mainly elderly people with comorbidity. Arabs have HLA allele and haplotype distribution that is different from other ethnicities, for example, the HLA-A2, B50, DR7 alleles and haplotype are found mainly in Arabs.[<xref rid="ref8" ref-type="bibr">8</xref>] Up to our knowledge, this is the first report on HLA associations with MERS infection. Our results demonstrate the association of severe MERS with HLA Class II alleles, namely DRB1*11:01 and DQB1*02:02. These alleles are also common in the Korean population[<xref rid="ref9" ref-type="bibr">9</xref>] where the second biggest outbreak of MERS infection occurred.[<xref rid="ref10" ref-type="bibr">10</xref>]</p><p>Multiple logistic regression analysis revealed no association between any of the HLA alleles and 28-day mortality (data not shown).</p><p>Conflicting results on HLA association were reported in SARS infection; a closely related emerging corona virus. While Xiong <italic>et al</italic>. and Ng <italic>et al</italic>.[<xref rid="ref5" ref-type="bibr">5</xref><xref rid="ref11" ref-type="bibr">11</xref>] reported no HLA associations, others showed association with HLA-A*46:01.[<xref rid="ref6" ref-type="bibr">6</xref>]</p></sec><sec sec-type="conclusion" id="sec1-4"><title>Conclusion</title><p>Here, we show association between severe MERS infection and HLA Class II alleles. Our sample size is small and this is one of the major limitations of this study. 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