Cytokines BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand) and their role in autoimmune diseases


Authors: O. Kryštůfková
Authors‘ workplace: Revmatologický ústav, Praha
Published in: Čes. Revmatol., 16, 2008, No. 1, p. 9-15.
Category: Overview Reports

Overview

B-lymphocytes play a significant role in pathogenesis of autoimmune diseases, and they are the target cells in therapy of resistant forms of connective tissue diseases (CTD). Cytokine BAFF (B-cell activating factor) supports maturation and survival of various differentiation stages of B-lymphocytes including autoreactive clones. The functions of BAFF are complex, since it has three receptors, two of which are shared with another ligand called APRIL (a proliferation-inducing ligand). These are BAFF-R (BAFF receptor), BCMA (B-cell maturation antigen) and TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor), and are differentially expressed in various stages of B-cells maturation. The fact that high levels of cytokines BAFF and APRIL in serum and expression in affected organs have been found in patients with various connective tissue diseases, such as primary Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis or dermatomyositis/polymyositis indicates biological significance of these cytokines in pathogenesis of CTD. Abnormal levels of BAFF have correlated with the activity of disease or with the positivity of autoantibodies or their titer. Based on these findings and experience with neutralization of BAFF by means of antibodies or receptors in mice models of autoimmune diseases, this cytokine has become potential therapeutic target. The block of BAFF can be preferable to induction of B-lymphocytes depletion by antibodies against the molecule CD20 (e.g. rituximab), which can not be found on the surface of all differentiation stages of B-lymphocytes. It has been found out, that rituximab therapy leads to elevation of BAFF levels in serum, what could lead to proliferation of autoreactive clones in the course of B-cells repopulation. At the present time, the monoclonal antibody against BAFF – belimumab and recombinant receptor TACI fused Ig - atacicept and BAFF-R-Ig (BR3-Fc) are successfully being studied in clinical trials.

Key words:
BAFF, APRIL, BAFF receptor, BCMA, TACI, systemic rheumatic diseases


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Labels
Dermatology & STDs Paediatric rheumatology Rheumatology
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