{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:15:06Z","timestamp":1777518906130,"version":"3.51.4"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20ek0410053"],"award-info":[{"award-number":["JP20ek0410053"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Specific HLA class II alleles are associated with susceptibility to systemic lupus erythematosus (SLE). The role of HLA class II molecules in SLE pathogenesis remains unclear, although anti\u2010DNA antibodies are specific to SLE and correlate with disease activity. We previously demonstrated that misfolded proteins bound to HLA class II molecules are specific targets for the autoantibodies produced in autoimmune diseases. This study was undertaken to validate our hypothesis that DNA binds to HLA class II molecules in a manner similar to that of misfolded proteins and that DNA bound to HLA class II molecules is involved in SLE pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the binding of DNA to HLA class II molecules, as well as the response of cells expressing anti\u2010DNA B cell receptors (BCRs) to cells expressing the DNA\/HLA class II complex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Efficient binding of DNA to HLA class II molecules was observed in risk alleles of SLE, such as HLA\u2013DRB1*15:01. The efficiency of DNA binding to each HLA\u2013DR allele was positively associated with the risk of SLE conferred by the HLA\u2013DR allele. In addition, reporter cells carrying anti\u2010DNA BCRs were activated by cells expressing DNA\/HLA class II complexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results provide evidence that DNA bound to HLA class II molecules is involved in SLE pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41897","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T02:01:52Z","timestamp":1624500112000},"page":"105-111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Anti\u2013Double\u2010Stranded DNA Antibodies Recognize DNA Presented on HLA Class II Molecules of Systemic Lupus Erythematosus Risk Alleles"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2521-246X","authenticated-orcid":false,"given":"Hideaki","family":"Tsuji","sequence":"first","affiliation":[{"name":"Kyoto University, Kyoto, Japan; World Premier International Immunology Frontier Research Center Osaka University, Suita, Japan, and Research Institute for Microbial Diseases, Osaka University  Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichiro","family":"Ohmura","sequence":"additional","affiliation":[{"name":"Kyoto University, Kyoto, Japan (current address: Kobe City Medical Center General Hospital, Kobe, Japan) : Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Jin","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, Osaka University  Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Naito","sequence":"additional","affiliation":[{"name":"Kyoto University, Kyoto, Japan; World Premier International Immunology Frontier Research Center Osaka University, Suita, Japan, and Research Institute for Microbial Diseases, Osaka University  Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-3437","authenticated-orcid":false,"given":"Noriko","family":"Arase","sequence":"additional","affiliation":[{"name":"Osaka University Graduate School of Medicine  Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Kohyama","sequence":"additional","affiliation":[{"name":"World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan, and Research Institute for Microbial Diseases Osaka University  Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadahiro","family":"Suenaga","sequence":"additional","affiliation":[{"name":"World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan, and Research Institute for Microbial Diseases Osaka University  Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhei","family":"Sakakibara","sequence":"additional","affiliation":[{"name":"World Premier International Immunology Frontier Research Center Osaka University  Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuta","family":"Kochi","sequence":"additional","affiliation":[{"name":"RIKEN Center for Integrative Medical Sciences, Yokohama, Japan, and Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0311-8472","authenticated-orcid":false,"given":"Yukinori","family":"Okada","sequence":"additional","affiliation":[{"name":"World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan; Osaka University Graduate School of Medicine Suita, Japan and RIKEN Center for Integrative Medical Sciences  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"RIKEN Center for Integrative Medical Sciences  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Kikutani","sequence":"additional","affiliation":[{"name":"World Premier International Immunology Frontier Research Center Osaka University  Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akio","family":"Morinobu","sequence":"additional","affiliation":[{"name":"Kyoto University, Kyoto, Japan (current address: Kobe City Medical Center General Hospital, Kobe, Japan) : Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuneyo","family":"Mimori","sequence":"additional","affiliation":[{"name":"Kyoto University, Kyoto, Japan (current address: Kobe City Medical Center General Hospital, Kobe, Japan) : Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-3166","authenticated-orcid":false,"given":"Hisashi","family":"Arase","sequence":"additional","affiliation":[{"name":"World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan; Research Institute for Microbial Diseases Osaka University, Suita, Japan, and Center for Infectious Disease Education and Research Osaka University  Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.69"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes427"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1995.tb44553.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1401105111"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-08-593624"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40170"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3754"},{"key":"e_1_2_7_9_1","first-page":"115","article-title":"Enhanced major histocompatibility complex (MHC) class II antigen expression in lupus nephritis","volume":"19","author":"Cheah PL","year":"1997","journal-title":"Malays J Pathol"},{"key":"e_1_2_7_10_1","first-page":"36","article-title":"IFN\u2010\u03b3, CXCL16, uPAR: potential biomarkers for systemic lupus erythematosus","volume":"36","author":"Wen S","year":"2018","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.4049\/jimmunol.153.4.1665","article-title":"Ligand motifs of HLA\u2010DRB5*0101 and DRB1*1501 molecules delineated from self\u2010peptides","volume":"153","author":"Vogt AB","year":"1994","journal-title":"J Immunol"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16681-y"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070884"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199902)42:2<268::AID-ANR8>3.0.CO;2-K"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI137866"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0798-781"}],"container-title":["Arthritis &amp; 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