The Role of B Cell-Activating Factor System in Autoimmune Diseases: Mechanisms, Disease Implications, and Therapeutic Advances

The B cell-activating factor (BAFF) system is crucial in both adaptive and innate immunity, contributing to autoimmune diseases like systemic lupus erythematosus, Sjögren’s syndrome, bullous pemphigoid, pemphigus vulgaris, and alopecia areata through dysregulated B and T cell functions. Overexpression of the BAFF system is linked to increased autoantibody levels and disease activity. BAFF-targeted therapies have shown effectiveness in reducing disease activity, particularly in SLE and SS. Challenges include differences in receptor expression across species and context-dependent signaling. Promising strategies, such as combining rituximab and belimumab, are emerging for refractory cases. Further research is needed to understand BAFF-mediated interactions and to develop precise treatments, emphasizing the need for disease-specific clinical trials.