{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T08:44:28Z","timestamp":1771663468638,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T00:00:00Z","timestamp":1209081600000},"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":[[2008,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess whether R788, an orally bioavailable small molecule inhibitor of spleen tyrosine kinase (Syk)\u2013dependent signaling, could modulate disease in lupus\u2010prone (NZB \u00d7 NZW)F<jats:sub>1<\/jats:sub> (NZB\/NZW) mice via inhibition of Fc receptor (FcR) and B cell receptor signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>R788 was administered to NZB\/NZW mice before and after disease onset. Proteinuria, blood urea nitrogen levels, and autoantibody titers were examined periodically, and overall survival and renal pathologic features were assessed following long\u2010term treatment (24\u201334 weeks). The distribution and immunophenotype of various splenic T cell and B cell subpopulations were evaluated at the time of study termination. Arthus responses in NZB\/NZW mice pretreated with R788 or Fc\u2010blocking antibody (anti\u2010CD16\/32) were also examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>When R788 was administered prior to or after disease onset, it delayed the onset of proteinuria and azotemia, reduced renal pathology and kidney infiltrates, and significantly prolonged survival of lupus\u2010prone NZB\/NZW mice; autoantibody titers were minimally affected throughout the study. Dose\u2010dependent reductions in the numbers of CD4+ activated T cells expressing high levels of CD44 or CD69 were apparent in spleens from R788\u2010treated mice. Minimal effects on the numbers of naive T cells expressing CD62 ligand and total CD8+ T cells per spleen were observed following long\u2010term drug treatment. R788 pretreatment resulted in reduced Arthus responses in NZB\/NZW mice, similar to results obtained in mice pretreated with FcR\u2010blocking antibody.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrate that a novel Syk\u2010selective inhibitor prevents the development of renal disease and treats established murine lupus nephritis. These data suggest that Syk inhibitors may be of therapeutic benefit in human lupus and related disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.23428","type":"journal-article","created":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T20:48:12Z","timestamp":1209156492000},"page":"1433-1444","source":"Crossref","is-referenced-by-count":146,"title":["An orally bioavailable spleen tyrosine kinase inhibitor delays disease progression and prolongs survival in murine lupus"],"prefix":"10.1002","volume":"58","author":[{"given":"Frances Rena","family":"Bahjat","sequence":"first","affiliation":[]},{"given":"Polly 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