{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:36:41Z","timestamp":1792021001150,"version":"4.4.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17ek0109104h0003, 17ek0109121h0003, 20ek0109360h003"],"award-info":[{"award-number":["17ek0109104h0003, 17ek0109121h0003, 20ek0109360h003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["JP20FC1044, JP17K09967, JP21K08435"],"award-info":[{"award-number":["JP20FC1044, JP17K09967, JP21K08435"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP17K09967, JP21K08435"],"award-info":[{"award-number":["JP17K09967, JP21K08435"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003837","name":"Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n \n Disease relapse remains a major problem in the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In European populations,\n HLA-DPB1*04:01<\/jats:italic>\n is associated with both susceptibility and relapse risk in proteinase 3-ANCA positive AAV. In a Japanese population, we previously reported an association between\n HLA-DRB1*09:01<\/jats:italic>\n and\n DQB1*03:03<\/jats:italic>\n with susceptibility to, and\n DRB1*13:02<\/jats:italic>\n with protection from, myeloperoxidase-ANCA positive AAV (MPO-AAV). Subsequently, the association of\n DQA1*03:02<\/jats:italic>\n , which is in strong linkage disequilibrium with\n DRB1*09:01<\/jats:italic>\n and\n DQB1*03:03<\/jats:italic>\n , with MPO-AAV susceptibility was reported in a Chinese population. However, an association between these alleles and risk of relapse has not yet been reported. Here, we examined whether\n HLA-class II<\/jats:italic>\n is associated with the risk of relapse in MPO-AAV.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n First, the association of\n HLA-DQA1*03:02<\/jats:italic>\n with susceptibility to MPO-AAV and microscopic polyangiitis (MPA) and its relationship with previously reported\n DRB1*09:01<\/jats:italic>\n and\n DQB1*03:03<\/jats:italic>\n were examined in 440 Japanese patients and 779 healthy controls. Next, the association with risk of relapse was analyzed in 199 MPO-ANCA positive, PR3-ANCA negative patients enrolled in previously reported cohort studies on remission induction therapy. Uncorrected P values (P\n uncorr<\/jats:sub>\n ) were corrected for multiple comparisons in each analysis using the false discovery rate method.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The association of\n DQA1*03:02<\/jats:italic>\n with susceptibility to MPO-AAV and MPA was confirmed in a Japanese population (MPO-AAV: P\n uncorr<\/jats:sub>\n =5.8x10\n -7<\/jats:sup>\n , odds ratio [OR] 1.74, 95% confidence interval [CI] 1.40\u20132.16, MPA: P\n uncorr<\/jats:sub>\n =1.1x10\n -5<\/jats:sup>\n , OR 1.71, 95%CI 1.34\u20132.17).\n DQA1*03:02<\/jats:italic>\n was in strong linkage disequilibrium with\n DRB1*09:01<\/jats:italic>\n and\n DQB1*03:03<\/jats:italic>\n , and the causal allele could not be determined using conditional logistic regression analysis. Relapse-free survival was shorter with nominal significance in carriers of\n DRB1*09:01<\/jats:italic>\n (P\n uncorr<\/jats:sub>\n =0.049, Q=0.42, hazard ratio [HR]:1.87),\n DQA1*03:02<\/jats:italic>\n (P\n uncorr<\/jats:sub>\n =0.020, Q=0.22, HR:2.11) and\n DQB1*03:03<\/jats:italic>\n (P\n uncorr<\/jats:sub>\n =0.043, Q=0.48, HR:1.91) than in non-carriers in the log-rank test. Conversely, serine carriers at position 13 of HLA-DR\u03b21 (HLA-DR\u03b21_13S), including\n DRB1*13:02<\/jats:italic>\n carriers, showed longer relapse-free survival with nominal significance (P\n uncorr<\/jats:sub>\n =0.010, Q=0.42, HR:0.31). By combining\n DQA1*03:02<\/jats:italic>\n and HLA-DR\u03b21_13S, a significant difference was detected between groups with the highest and lowest risk for relapse (P\n uncorr<\/jats:sub>\n =0.0055, Q=0.033, HR:4.02).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n HLA-class II<\/jats:italic>\n is associated not only with susceptibility to MPO-AAV but also with risk of relapse in the Japanese population.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2023.1119064","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:09:03Z","timestamp":1678234143000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Association of HLA-class II alleles with risk of relapse in myeloperoxidase-antineutrophil cytoplasmic antibody positive vasculitis in the Japanese 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