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Yet, the immunobiologic significance of persistent ACPA production at the cellular level is poorly understood. This study was undertaken to investigate the representation of ACPA\u2010expressing switched\u2010memory B cells in RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a cross\u2010sectional study of RA patients, we investigated the presence of continued defects in immune homeostasis as a function of disease activity. Using an enzyme\u2010linked immunosorbent assay (ELISA) and a sensitive multiplex bead\u2010based immunoassay, we characterized fine binding antibody specificities in sera, synovial fluid (SF), and B cell culture supernatants. In this manner, we determined the frequency and epitope reactivity patterns of ACPAs produced by SF B cells and switched\u2010memory blood B cells and compared the latter to serum ACPA levels and disease activity scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cultured B cells from SF were shown to spontaneously secrete ACPAs, while constitutive IgG autoantibody production by peripheral blood mononuclear cells (PBMCs) was substantially less frequent. After in vitro stimulation, PBMCs secreted IgG ACPA that was overwhelmingly from switched\u2010memory B cells, across all patient groups treated with methotrexate and\/or a tumor necrosis factor inhibitor. Intriguingly, the frequencies of ACPA\u2010expressing switched\u2010memory B cells significantly correlated with serum IgG anti\u2013cyclic citrullinated peptide 3 (r\u2009=\u20090.57, <jats:italic>P<\/jats:italic>\u2009=\u20090.003). Moreover, treatment\u2010induced clinical remission had little or no effect on the circulating burden of switched\u2010memory ACPA\u2010expressing B cells, in part explaining the continued dysregulation of humoral immunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings rationalize why therapeutic cessation most often results in disease reactivation and clinical flare. Hence, a clinical disease activity score is not a reliable indicator of the resolution of pathologic recirculating B cell autoimmunity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40053","type":"journal-article","created":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T14:12:53Z","timestamp":1485267173000},"page":"1176-1186","source":"Crossref","is-referenced-by-count":40,"title":["Persistence of Disease\u2010Associated Anti\u2013Citrullinated Protein Antibody\u2013Expressing Memory B Cells in Rheumatoid Arthritis in Clinical Remission"],"prefix":"10.1002","volume":"69","author":[{"given":"Adam J.","family":"Pelzek","sequence":"first","affiliation":[{"name":"New York University School of Medicine New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Gr\u00f6nwall","sequence":"additional","affiliation":[{"name":"New York University School of Medicine New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"New York University School of Medicine New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"New York University School of Medicine New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"McGeachy","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Moreland","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F. 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