{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:29:51Z","timestamp":1792553391670,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T00:00:00Z","timestamp":1453680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Special Fund for Research Grants (ELKE)"},{"name":"University of Thessaly, Greece"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Breg cells, a regulatory cell subset that produces interleukin\u201010 (IL\u201010), play a significant role in suppressing autoimmune responses and preventing autoimmunity. This study was undertaken to examine the number and function of Breg cells in patients with systemic sclerosis (SSc), a disease with many autoantibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty\u2010five patients with SSc (12 with early SSc, 33 with established disease including 16 with SSc\u2010associated pulmonary fibrosis [PF]), 12 healthy control subjects, and 10 patients with rheumatoid arthritis (RA)\u2013associated PF were studied. The phenotypes of immature\/transitional Breg cells (CD19+CD24<jats:sup>high<\/jats:sup>CD38<jats:sup>high<\/jats:sup>) and memory Breg cells (CD19+CD27+CD24<jats:sup>high<\/jats:sup>) were evaluated by flow cytometry. The function of Breg cells was assessed by measuring the production of IL\u201010 after B cell activation. In addition, activation of p38 MAPK and STAT\u20103 was measured following stimulation of the cells with B cell receptor (BCR) and Toll\u2010like receptor 9 (TLR\u20109).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Percentages of memory Breg cells were decreased in patients with early SSc (mean\u2009\u00b1\u2009SEM 1.85\u2009\u00b1 0.38%), those with established SSc (1.6\u2009\u00b1\u20090.88%), those with SSc\u2010associated PF (1.52\u2009\u00b1\u20090.17%), and those with RA\u2010associated PF (1.58\u2009\u00b1\u20090.26%), compared to healthy controls (6.3\u2009\u00b1\u20090.49%; each <jats:italic>P<\/jats:italic> &lt; 0.001). Percentages of transitional Breg cells were also decreased. Expression of IL\u201010 by Breg cells after stimulation with TLR\u20109 was impaired in patients with SSc, particularly those with SSc\u2010associated PF. Activation of STAT\u20103 and p38 MAPK was impaired in naive and memory B cells from patients with SSc after stimulation with BCR and TLR\u20109. Expression of the stimulatory CD19 receptor was increased in B cells and also increased, to a lesser extent, in Breg cells from patients with SSc compared to healthy controls. Percentages of memory B cells were decreased in patients with SSc, particularly in those with SSc\u2010associated PF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first study to demonstrate that Breg cells are phenotypically and functionally impaired in patients with SSc. Furthermore, in SSc, B cells exhibit impaired p38 MAPK and STAT\u20103 activation upon stimulation with BCR and TLR\u20109. The findings of decreased numbers of Breg cells along with increased expression of CD19 support the idea of B cell autoaggression acting as an immunopathogenic mediator in SSc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39437","type":"journal-article","created":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T12:51:02Z","timestamp":1443444662000},"page":"494-504","source":"Crossref","is-referenced-by-count":145,"title":["Breg Cells Are Numerically Decreased and Functionally Impaired in Patients With Systemic Sclerosis"],"prefix":"10.1002","volume":"68","author":[{"given":"Athanasios","family":"Mavropoulos","sequence":"first","affiliation":[{"name":"University of Thessaly Larissa Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora","family":"Simopoulou","sequence":"additional","affiliation":[{"name":"University of Thessaly Larissa 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