Belimumab

Systemic lupus erythematosus (SLE) and lupus nephritis, a common and serious manifestation of SLE, are autoimmune disorders characterized by the presence of autoreactive B lymphocytes (B cells), which promotes the production of autoantibodies that cause inflammation and progressive and irreversible tissue damage. One of the key cytokines involved in B cell homeostasis and survival is B lymphocyte stimulator protein (BLyS), which is a member of tumour necrosis factor (TNF) superfamily of cytokines. While the contribution of BLyS to the pathophysiology of autoimmune diseases is not fully understood, BLyS has been identified as a key therapeutic target for the treatment of SLE as BLyS levels are elevated in patients with SLE along with other autoimmune diseases.

Belimumab is an antibody directed against BLyS: it selectively binds BLyS with high affinity, neutralizes it, and blocks its interaction with B cell receptors - transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), B-cell maturation antigen (BCMA), and BLyS receptor 3 (BR3). Belimumab ultimately inhibits the survival of B cells, promotes apoptosis, and reduces the differentiation and maturation of B cells into immunoglobulin-producing plasma cells.