The BAFF / APRIL system as therapeutic target in multiple sclerosis.

The complex system of BAFF (B-cell-activating factor of the TNF family) and APRIL (A proliferation-inducing ligand) has been studied in animal models of autoimmune diseases such as those resembling human systemic lupus erythematosus and Sjogren's syndrome and multiple sclerosis (MS). Accumulating evidence suggests that BAFF and APRIL have a physiological role in B cell immunity regulation, however inappropriate production of these factors may represent a key event which disrupts immune tolerance which is associated with systemic autoimmune diseases. We provide an update on the latest studies of the BAFF/APRIL system in multiple sclerosis, as well as on related clinical trials. Experimental and clinical evidence suggests that increased BAFF levels may interfere directly and indirectly with B cell immunity; this can lead to breakdown of immune tolerance, the production of autoantibodies and continuous local intracerebral inflammation and brain tissue destruction. A more comprehensive understanding of the cell/molecular mechanism immune reactions specifically regulated by BAFF/APRIL in MS would better elucidate the specific cell phenotype targeted by actual anti-BAFF/APRIL therapies; this may enable the identification of either specific biomarkers of MS subgroups that would benefit of anti-BAFF/APRIL treatments or new targets of MS-specific anti-BAFF/APRIL therapies.