{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:33:24Z","timestamp":1791506004288,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,12,28]],"date-time":"2009-12-28T00:00:00Z","timestamp":1261958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To understand the effects of long\u2010term BLyS inhibition in human systemic lupus erythematosus (SLE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventeen patients with SLE who were enrolled in a clinical trial of belimumab, a BLyS\u2010specific inhibitor, plus standard of care therapy were studied. Phenotypic analysis of lymphocytes was performed using flow cytometry. Circulating antibody\u2010secreting cells were enumerated using enzyme\u2010linked immunospot assay. Serum was analyzed by enzyme\u2010linked immunosorbent assay using an antibody that recognizes products of the V<jats:sub>H<\/jats:sub>4\u201334 gene. Lymphocyte counts, Ig levels, and anti\u2013double\u2010stranded DNA antibody levels were available as part of the clinical trial analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Samples were collected on days 0, 84, 168, 365, and 532 and after day 730. The total number of B cells started to decrease from baseline between days 84 and 168. This was due to a decrease in naive and transitional B cells. CD27+IgD+ memory B cells and plasmablasts decreased only after 532 days, whereas CD27+IgD\u2212 memory B cells were not affected, and there were no changes in T cells. Serum IgM levels began to decline between days 84 and 168, but there were no changes in serum levels of IgG, IgG anti\u2010DNA antibodies, or V<jats:sub>H<\/jats:sub>4\u201334 antibodies during the study. SLE patients had more IgM\u2010, IgG\u2010, and autoantibody\u2010producing B cells than did normal controls on day 0. There was only a modest decrease in the frequency of total IgM\u2010producing, but not IgG\u2010producing, cells on days 365 and 532, consistent with the phenotypic and serologic data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data confirm the dependence of newly formed B cells on BLyS for survival in humans. In contrast, memory B cells and plasma cells are less susceptible to selective BLyS inhibition.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.27189","type":"journal-article","created":{"date-parts":[[2009,12,28]],"date-time":"2009-12-28T21:05:46Z","timestamp":1262034346000},"page":"201-210","source":"Crossref","is-referenced-by-count":207,"title":["Effect of long\u2010term belimumab treatment on b cells in systemic lupus erythematosus: Extension of a phase II, double\u2010blind, placebo\u2010controlled, dose\u2010ranging study"],"prefix":"10.1002","volume":"62","author":[{"given":"Annett 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