{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:51:18Z","timestamp":1788371478760,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,5,10]],"date-time":"2017-05-10T00:00:00Z","timestamp":1494374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Dutch Arthritis Foundation","award":["09-1-302 and 13-2-301"],"award-info":[{"award-number":["09-1-302 and 13-2-301"]}]},{"name":"Bristol-Myers Squibb, France"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Bruton's tyrosine kinase (BTK) transmits crucial survival signals from the B cell receptor (BCR) in B cells. Pharmacologic BTK inhibition effectively diminishes disease symptoms in mouse models of autoimmunity; conversely, transgenic BTK overexpression induces systemic autoimmunity in mice. We undertook this study to investigate BTK expression and activity in human B cells in the context of autoimmune disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using intracellular flow cytometry, we quantified BTK expression and phosphorylation in subsets of peripheral blood B cells from 30 patients with rheumatoid arthritis (RA), 26 patients with primary Sj\u00f6gren's syndrome (SS), and matched healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In circulating B cells, BTK protein expression levels correlated with BTK phosphorylation. BTK expression was up\u2010regulated upon BCR stimulation in vitro and was significantly higher in CD27+ memory B cells than in CD27\u2212IgD+ naive B cells. Importantly, BTK protein and phospho\u2010BTK were significantly increased in B cells from anti\u2013citrullinated protein antibody (ACPA)\u2013positive RA patients but not in B cells from ACPA\u2010negative RA patients. BTK was increased both in naive B cells and in memory B cells and correlated with frequencies of circulating CCR6+ Th17 cells. Likewise, BTK protein was increased in B cells from a major fraction of patients with primary SS and correlated with serum rheumatoid factor levels and parotid gland T cell infiltration. Interestingly, targeting T cell activation in patients with primary SS using the CTLA\u20104Ig fusion protein abatacept restored BTK protein expression in B cells to normal levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data indicate that autoimmune disease in humans is characterized by enhanced BTK activity, which is linked not only to autoantibody formation but also to T cell activity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40059","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T15:17:06Z","timestamp":1485875826000},"page":"1313-1324","source":"Crossref","is-referenced-by-count":107,"title":["Enhanced Bruton's Tyrosine Kinase Activity in Peripheral Blood B Lymphocytes From Patients With Autoimmune Disease"],"prefix":"10.1002","volume":"69","author":[{"given":"Odilia B. 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