Therapeutic Targeting of B Lymphocyte Stimulator (BLyS) in the Rheumatic Diseases

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Abstract:

B lymphocyte stimulator (BLyS) is a vital B cell survival factor. Overexpression of BLyS in mice can lead to clinical and serological features of systemic lupus erythematosus (SLE) and Sjögren' s syndrome (SS). Treatment with BLyS antagonists of mice with established SLE ameliorates disease progression and enhances survival. Moreover, similar treatment of mice with inflammatory arthritis ameliorates the ongoing inflammation and subsequent joint destruction. In humans, BLyS overexpression is common in patients with several rheumatic diseases, including SLE, rheumatoid arthritis (RA), Sjogren' s syndrome, scleroderma, Wegener' s granulomatosis, and ANCA-associated vasculitis. Results from phase-II clinical trials with a BLyS antagonist in human SLE and RA have shown the antagonist to have biological and clinical activity along with a favorable safety profile. These features collectively point to BLyS as an attractive therapeutic target in human rheumatic diseases.

Keywords: APRIL; B cells; B lymphocyte stimulator (BLyS); rheumatoid arthritis; Sjogren' s syndrome; systemic lupus erythematosus

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187153006779025801

Affiliations: 1: Division of Rheumatology, University of Southern California, 2011 Zonal Ave. HMR 711, Los Angeles, CA 90033, USA.

Publication date: 2006-12-01

More about this publication?
  • This journal is devoted to timely reviews of experimental and clinical studies in the field of endocrine, metabolic, and immune disorders. Specific emphasis is placed on humoral and cellular targets for natural, synthetic, and genetically engineered drugs that enhance or impair endocrine, metabolic, and immune parameters and functions. Topics related to the neuroendocrine-immune axis are given special emphasis in view of the growing interest in stress-related, inflammatory, autoimmune, and degenerative disorders.
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