BAFF: Autoimmune Disease Drug Target in Cytokines & Growth factors

Introduction of BAFF as a Cytokine

BAFF (B lymphocyte activating factor of the tumour necrosis factor family) is a vital homeostatic cytokine for B cells that helps regulate both innate and adaptive immune responses. BAFF is a member of the tumour necrosis factor (TNF) family and is expressed on the surface of monocytes, dendritic cells (DC), neutrophils, stromal cells, activated T cells, malignant B cells and epithelial cells. BAFF binds to three different receptors, BAFF-R, TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BCMA (B cell maturation
protein), that are expressed differentially at various times during B cell ontogeny.

BAFF as Drug Targets in Autoimmune Disease

Increased serum levels of BAFF are found in a number of different autoimmune diseases, and BAFF is found in inflammatory
sites in which there is lymphoid neogenesis. BAFF antagonism has been used in several autoimmune disease models, resulting in B cell depletion, decreased activation of T cells and dendritic cells (DC) and a reduction in the overall inflammatory burden. BAFF, through its interaction with BAFF-R, is required for survival of late transitional, marginal zone and mature naive B cells, all of which are depleted by BAFF blockade. Through their interactions with TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BCMA (B cell maturation protein), BAFF support the survival of at least some subsets of plasma cells; blockade of both cytokines results in a decrease in serum levels of immunoglobulin (Ig)G. In contrast, BAFF is not required for the survival or reactivation of memory B cells or B1 cells. BAFF also helps DC maturation and interleukin (IL)-6 release and is required for proper formation of a follicular dendritic cell (FDC) network within germinal centres, although not for B cell affinity maturation. The clinical efficacy of BAFF blockade in animal models of autoimmunity may be caused both by the decline in the number of inflammatory cells and by the inhibition of DC maturation within target organs. Several strategies have been developed to block BAFF and in vivo.

Inhibition of BAFF as Drug Targets in Autoimmune Disease

Selective inhibition of BAFF can be achieved with a soluble BAFF-R-Ig fusion protein or with an antibody to BAFF; soluble TACI-Ig or BCMA-Ig fusion proteins can also block both BAFF. Clinical trials of a selective antibody to BAFF (Belimumab) and with the BAFF inhibitor TACI-Ig (Atacicept) are currently in progress. BAFF may be a therapeutic target in several different diseases,such as Rheumatoid arthritis (RA), Multiple sclerosis (MS), Sjögren's syndrome and SLE.

BAFF: Autoimmune Disease Drug Target in Cytokines & Growth factors: Reference

Moisini I, et al. BAFF: a local and systemic target in autoimmune diseases[J]. Clinical & Experimental Immunology, 2009, 158(2): 155-163.