Therapeutic targeting of B lymphocyte stimulator (BLyS) in the rheumatic diseases.
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), Sjögren'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.
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ABSTRACT: The B Lymphocyte Stimulator (BLyS) family of ligands and receptors regulates humoral immunity by controlling B lymphocyte survival and differentiation. Herein, we review the ligands and receptors of this family, their biological functions, and the biochemical processes through which they operate. Pre-immune B lymphocytes rely on BLyS signaling for their survival, whereas antigen experienced B lymphocytes generally interact more avidly with a homologous cytokine, A Proliferation Inducing Ligand (APRIL). The molecular basis for signaling via the three BLyS family receptors reveals complex interplay with other B lymphocyte signaling systems, affording the integration of selective and homeostatic processes. As our understanding of this system advances, molecular targets for manipulating humoral immunity in both health and disease should be revealed.Cell biochemistry and biophysics 12/2008; 53(1):1-16. · 3.34 Impact Factor
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ABSTRACT: A proliferation-inducing ligand (APRIL) is a tumor necrosis factor (TNF) superfamily member ligand that stimulates B cells in vitro and in vivo. It also plays an important role in T cell activation and survival. This study was conducted to evaluate serum levels of APRIL in patients with atopic dermatitis (AD) and vitiligo and their correlation with disease activity. A total of 100 subjects were included; these comprised 40 AD patients, 40 vitiligo patients, and 20 control subjects. Serum APRIL levels were measured and their relationships with the severity of AD and activity of vitiligo evaluated according to scores on the SCORAD (SCORing of Atopic Dermatitis) and VIDA (Vitiligo Disease Activity) indices, respectively. The serum level of APRIL was significantly higher in AD patients than in the control group. Serum APRIL in patients with severe AD showed a statistically significant difference with serum APRIL in patients with either mild or moderate AD. Serum APRIL was significantly higher in vitiligo patients than in the control group. Differences in serum APRIL among patients with different VIDA scores were significant only between patients with VIDA scores of +1 and +4. Statistically significant positive correlations emerged between serum APRIL and activity of AD (r = 0.939) and vitiligo (r = 0.740). APRIL may play a role in the pathogeneses of AD and vitiligo and could be used as an objective marker for the assessment of AD severity and vitiligo activity. Further studies are required to clarify the precise mechanism of APRIL in the pathogeneses of AD and vitiligo and to test the possible use of APRIL inhibitors as novel modalities of therapy.International journal of dermatology 12/2013; · 1.23 Impact Factor
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ABSTRACT: To investigate the levels of APRIL, BlyS and receptors as TACI, BCMA and BAFF-R in peripheral blood mononuclear cells (PBMC) of cryptococcal meningitis (CM) patients and its clinical significance. PBMC from 30 CM patients and 32 healthy controls were isolated. The mRNA levels of APRIL, BLyS and BLyS receptors were detected by fluorescent quantitation PCR. The effect of PBMC from CM patients on in vitro growth of Cryptococcus neoformans was compared in presence and absence of BLyS. PBMC of CM patients exhibited significantly lower BLyS, TACI and BCMA mRNA levels but significantly higher BAFF-R mRNA levels than controls. Growth of C. neoformans was significantly slower in presence of BLyS than its absence. Levels of BlyS and its receptors correlated with cryptococcal meningitis progression, and provide new clues for monitoring CM conditions and its effective therapy.Clinical biochemistry 11/2009; 43(4-5):397-400. · 2.02 Impact Factor