{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:16:22Z","timestamp":1777518982446,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,8,25]],"date-time":"2017-08-25T00:00:00Z","timestamp":1503619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005865","name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005865","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"}]},{"DOI":"10.13039\/100011313","name":"Tokyo Biochemical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011313","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Autoantibodies against myeloperoxidase (MPO) that are expressed in neutrophils play an important role in the pathogenesis of microscopic polyangiitis (MPA). We recently observed that misfolded cellular proteins are transported to the cell surface by HLA class II molecules and are targeted by autoantibodies in patients with rheumatoid arthritis or antiphospholipid syndrome, suggesting that HLA class II molecules play an important role in autoantibody recognition. The aim of this study was to address the role of HLA class II molecules in the cell surface expression of MPO in patients with MPA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The association of MPO with HLA\u2013DR was analyzed using MPO and HLA\u2013DR transfectants as well as neutrophils from healthy donors and patients with MPA. Autoantibody binding to the MPO\/HLA\u2013DR complex was analyzed by flow cytometry. The association of MPO with HLA\u2013DR was assessed using the immunoprecipitation technique. The function of MPO\u2013antineutrophil cytoplasmic antibody (ANCA) was assessed using a neutrophil\u2010like cell line expressing HLA\u2013DR and MPO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MPO protein was detected on the cell surface in the presence of HLA\u2013DR, and the MPO\/HLA\u2013DR complex was recognized by MPO\u2010ANCA. A competitive inhibition assay suggested that MPO associated with HLA\u2013DR expresses cryptic autoantibody epitopes for MPO\u2010ANCA. Autoantibody binding to the MPO\/HLA\u2013DR complex was correlated with disease susceptibility conferred by each HLA\u2013DR allele, suggesting that the MPO\/HLA\u2013DR complex is involved in the pathogenicity of MPA. Indeed, MPO\u2013HLA class II complexes were detected in neutrophils from a patient with MPA as well as in cytokine\u2010stimulated neutrophils from healthy donors. Moreover, MPO\u2010ANCA stimulated MPO\/HLA\u2013DR complex\u2013expressing HL\u201060 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that MPO complexed with HLA class II molecules is involved in the pathogenesis of MPA as a target for MPO\u2010ANCA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40170","type":"journal-article","created":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T12:46:41Z","timestamp":1496407601000},"page":"2069-2080","source":"Crossref","is-referenced-by-count":30,"title":["Myeloperoxidase\/HLA Class II Complexes Recognized by Autoantibodies in Microscopic Polyangiitis"],"prefix":"10.1002","volume":"69","author":[{"given":"Ryosuke","family":"Hiwa","sequence":"first","affiliation":[{"name":"World Premier International Immunology Frontier Research Center and Osaka University, Suita, Japan, and Kyoto University Kyoto 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