{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:30:11Z","timestamp":1772497811166,"version":"3.50.1"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Grant-In-Aid for Scientific Research from the Ministry of Health, Labor and Welfare of Japan","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]},{"name":"Grant-In-Aid for the Ministry of Education, Culture, Sports, Science and Technology of Japan","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]},{"DOI":"10.13039\/501100004019","name":"National Institute of Occupational Safety and Health, Japan","doi-asserted-by":"crossref","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}],"id":[{"id":"10.13039\/501100004019","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>B cell depletion by rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, peripheral B cell phenotypes and the selection criteria for RTX therapy in AAV remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Phenotypic characterization of circulating B cells was performed by 8-color flow cytometric analysis in 54 newly diagnosed AAV patients (20 granulomatosis with polyangiitis and 34 microscopic polyangiitis). Patients were considered eligible to receive intravenous cyclophosphamide pulse (IV-CY) or RTX. All patients also received high-dose glucocorticoids (GC). We assessed circulating B cell phenotypes and evaluated the efficacy after 6\u2009months of treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There were no significant differences in the rate of clinical improvement, relapses, or serious adverse events between patients receiving RTX and IV-CY. The rate of Birmingham Vasculitis Activity Score (BVAS) improvement at 6\u2009months tended to be higher in the RTX group than in the IV-CY group. The proportion of effector or class-switched memory B cells increased in 24 out of 54 patients (44%). The proportions of peripheral T and B cell phenotypes did not correlate with BVAS at baseline. However, among peripheral B cells, the proportion of class-switched memory B cells negatively correlated with the rate of improvement in BVAS at 6\u2009months after treatment initiation (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2212\u20090.28,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04). Patients with excessive B cell differentiation were defined as those in whom the proportion of class-switched memory B cells or IgD\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD27\n                      <jats:sup>\u2212<\/jats:sup>\n                      B cells among all B cells was &gt;\u20092 SDs higher than the mean in the HCs. The rate of BVAS remission in patients with excessive B cell differentiation was significantly lower than that in patients without. In patients with excessive B cell differentiation, the survival rate, the rate of BVAS-remission, and dose reduction of GC were significantly improved in the RTX group compared to those in the IV-CY group after 6\u2009months of treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The presence of excessive B cell differentiation was associated with treatment resistance. However, in patients with circulating B cell abnormality, RTX was effective and increased survival compared to IV-CY. The results suggest that multi-color flow cytometry may be useful to determine the selection criteria for RTX therapy in AAV patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-020-02215-x","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T07:04:28Z","timestamp":1592204668000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Favorable efficacy of rituximab in ANCA-associated vasculitis patients with excessive B cell differentiation"],"prefix":"10.1186","volume":"22","author":[{"given":"Yusuke","family":"Miyazaki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Nakayamada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiko","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Sakata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ippei","family":"Miyagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhisa","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7139","authenticated-orcid":false,"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"issue":"1","key":"2215_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/art.37715","volume":"65","author":"JC Jennette","year":"2013","unstructured":"Jennette JC, et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1\u201311.","journal-title":"Arthritis Rheum"},{"issue":"1","key":"2215_CR2","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1056\/NEJMoa020286","volume":"349","author":"D Jayne","year":"2003","unstructured":"Jayne D, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003;349(1):36\u201344.","journal-title":"N Engl J Med"},{"issue":"3","key":"2215_CR3","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1056\/NEJMoa0909905","volume":"363","author":"JH Stone","year":"2010","unstructured":"Stone JH, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221\u201332.","journal-title":"N Engl J Med"},{"issue":"3","key":"2215_CR4","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1056\/NEJMoa0909169","volume":"363","author":"RB Jones","year":"2010","unstructured":"Jones RB, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010;363(3):211\u201320.","journal-title":"N Engl J Med"},{"issue":"10","key":"2215_CR5","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1002\/art.40180","volume":"69","author":"S Kubo","year":"2017","unstructured":"Kubo S, et al. Peripheral immunophenotyping identifies three subgroups based on T cell heterogeneity in lupus patients. Arthritis Rheumatol. 2017;69(10):2029\u201337.","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"2215_CR6","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1093\/rheumatology\/kex012","volume":"57","author":"S Nakayamada","year":"2018","unstructured":"Nakayamada S, et al. Differential effects of biological DMARDs on peripheral immune cell phenotypes in patients with rheumatoid arthritis. 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Each subject provided a signed consent form.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"S. Nakayamada has received speaking fees from Bristol-Myers, Pfizer, Chugai, Astellas, Sanofi, GlaxoSmithKline, and Asahi-kasei and has received research grants from Mitsubishi-Tanabe, Novartis, and MSD. S. Kubo has received speaking fees from Bristol-Myers. Y. Tanaka has received consulting fees, speaking fees, and\/or honoraria from Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, and Santen and received research grants from Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, and Bristol-Myers. All other authors declare no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"141"}}