BAFF/BLyS inhibitors: A new prospect for treatment of systemic lupus erythematosus

Abstract

In November 2009, Human Genome Sciences and Glaxo‐Smith Kline [HGS (Rockville, Maryland) and GSK, respectively] announced that Belimumab, a neutralizing antibody to the tumour necrosis factor (TNF)‐like ligand, B‐cell activating factor (BAFF belonging to the TNF family, also named BLyS), met the primary endpoints in two phase III clinical trials in systemic lupus erythematosus (SLE, lupus). In March 2011, Belimumab was approved by the US Federal Drug Agency for treatment of SLE patients; this was followed in May with approval by the European Medicines Agency for use in the European Union. This is an exciting development as it is the first successful late‐stage clinical trial in SLE in over 40 years. In the light of this breakthrough, we review the key data and research outcomes and examine how blocking BAFF in patients with SLE significantly improves clinical outcomes. © 2012 IUBMB IUBMB Life, 64(7): 595–602, 2012

Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus

“…Several other BAFF-targeted therapeutics are currently in trials for the treatment of SLE and other inflammatory conditions (30). Given the importance of BAFF in SLE pathogenesis, its status as a treatment target, and the association of anti-BAFF autoantibodies with elevated IFN signature and proinflammatory SLE cytokines, it will be important for researchers and clinicians to factor the contribution of naturally occurring BAFFreactive autoantibodies into SLE research and treatment.…”

Autoimmune hepatitis: What must be said

“…The raised levels of IgG are labile to the degree that a decrease with remission is a reliable indicator of reduced hepatocellular inflammatory activity, and hence is a reliable test for efficacy of immunosuppressive therapy. Explanations for this hyper-IgG-emia, insufficient as they may be, include the production of serum autoantibodies (see below) and/or anti-idiotypic antibodies to these, both attributable are part to B-cell overdrive delivered by the B lymphocyte-activating factor (BAFF) which could be an integral part of the disease process, comparable with that reported in SLE (Fairfax et al, 2012). Presently however a systematic study of levels of BAFF in relapse and remission phases of AIH is not available.…”

CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co-cultured with BAFF-activated CD4+ T cells

“…BAFF plays an important role in autoimmune diseases (Davidson, 2012). The level of serum BAFF was elevated in patients with RA, systemic lupus erythematosus and Sjögren's syndrome (Fairfax et al, 2012;Liu and Davidson, 2011a). In CIA mice and the AA rat model, increased BAFF production contributes most significantly to the disease progression Chang et al, 2011a).…”

“…B cell activating factor belonging to the TNF family (BAFF) is a basic survival factor during B cell maturation in the spleen at a critical stage of B cell development and is produced by macrophages, neutrophils, monocytes and dendritic cells Davidson, 2011a, 2011b;Fairfax et al, 2012). BAFF exerts its activity by interacting with three receptors: transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), B-cell maturation antigen (BCMA) and BAFF receptor (BAFF-R) (Kayagaki et al, 2002).…”