{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:49:23Z","timestamp":1790102963746,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,6,3]],"date-time":"2004-06-03T00:00:00Z","timestamp":1086220800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Serum B lymphocyte stimulator (BLyS) is increased in autoimmune diseases, both in animal models and in humans. This study examined the effect of BLyS blockade in 3 animal models of lupus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Antibodies and lupus\u2010like disease manifestations were examined in mice after administration of a single injection of an adenoviral construct for the transmembrane activator and CAML interactor receptor (AdTACI) that produces high serum levels of TACI\u2010Fc fusion protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In C57BL\/6 (B6) <jats:italic>lpr\/lpr<\/jats:italic> mice (B6.<jats:italic>lpr\/lpr<\/jats:italic>), which were used to model autoimmunity in the absence of severe disease, treatment of younger mice with AdTACI prevented the development of hypergammaglobulinemia. In contrast, use of AdTACI for BLyS blockade had only transient effects on the levels of IgG in normal B6 mice. AdTACI blocked the development of autoantibodies in younger B6.<jats:italic>lpr\/lpr<\/jats:italic> mice and reversed the production of autoantibodies in older B6.<jats:italic>lpr\/lpr<\/jats:italic> mice, and also reduced the numbers of splenic plasma cells. In MRL.<jats:italic>lpr\/lpr<\/jats:italic> mice, which were used to examine disease manifestations, AdTACI reduced the extent of glomerulonephritis and proteinuria and improved survival, but had little effect on T cell infiltration and interstitial nephritis. However, in (NZB \u00d7 NZW)F<jats:sub>1<\/jats:sub> mice, AdTACI induced neutralizing anti\u2010TACI antibodies and failed to reduce the numbers of B cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BLyS blockade has little effect on IgG levels in normal mice, but reverses the production of spontaneously produced IgM and IgG autoantibodies in the setting of established autoimmunity. Blockade of BLyS ameliorates B cell\u2013dependent disease manifestations even in the MRL.<jats:italic>lpr\/lpr<\/jats:italic> model, but its effectiveness on autonomous T cell aspects of the disease is limited. Moreover, its effectiveness is neutralized by anti\u2010TACI antibodies when present. These results provide a basis for understanding the potential effects of BLyS blockade in human disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20290","type":"journal-article","created":{"date-parts":[[2004,6,3]],"date-time":"2004-06-03T17:01:59Z","timestamp":1086282119000},"page":"1884-1896","source":"Crossref","is-referenced-by-count":55,"title":["Control of spontaneous B lymphocyte autoimmunity with adenovirus\u2010encoded soluble 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