B cell activating factor (BAFF): Structure, functions, autoimmunity and clinical implications in Systemic Lupus Erythematosus (SLE)

The B cell activating factor (BAFF), or B lymphocyte stimulator (BLyS), is a B cell survival factor which supports autoreactive B cells and prevents their deletion. BAFF expression is closely linked with autoimmunity and is enhanced by genetic alterations and viral infections. Furthermore, BAFF seems to be involved in adipogenesis, atherosclerosis, neuro-inflammatory processes and ischemia reperfusion (I/R) injury. BAFF is commonly overexpressed in Systemic Lupus Erythematosus (SLE) and strongly involved in the pathogenesis of the disease. The relationship between BAFF levels, disease activity and damage accrual in SLE is controversial, but growing evidence is emerging on its role in renal involvement. Belimumab, a biologic BAFF inhibitor, has been the first biologic agent licensed for SLE therapy so far. As Rituximab (RTX) has been shown to increase BAFF levels following B cell depletion, the combination therapy of RTX plus belimumab (being evaluated in two RCT) seems to be a valuable option for several clinical scenarios. In this review we will highlight the growing body of evidence of immune and non-immune related BAFF expression in experimental and clinical settings. • BAFF overexpression is enhanced by genetic alterations and viral infections. • BAFF is expressed by myeloid cells as well as non-immune tissues, including kidney. • BAFF seems to be strongly involved in lupus pathogenesis and auto Ab production. • The relationship between BAFF levels and disease activity in SLE is discussed. • Belimumab, an anti-BAFF antibody, is the only biologic agent so far approved for SLE therapy.