The emerging role of BLyS/APRIL in autoimmune diseases: Biological characteristics, functions, and therapeutic...

Autoimmune diseases (AIDs) are common diseases in the world. Some cases are difficult to cure and can only delay the progression of the diseases. The B lymphocyte stimulator (BLyS)/a proliferation-inducing ligand (APRIL) plays an important role in B cell homeostasis, regulation of both innate and adaptive immune responses. After binding to their receptors, BLyS/APRIL primarily affects the survival and development of marginal, transitional, and mature B cells. Of note, elevated BLyS/APRIL is seen in many AIDs, such as systemic lupus erythematosus, rheumatoid arthritis, immunoglobulin A nephropathy, etc. Moreover, there is evidence that blocking these two cytokines can control the number of serum autoantibodies, promote the depletion of B lymphocytes, inhibit the activation of T cells and dendritic lymphocytes, and reduce inflammatory stress. Currently, some clinical studies are underway targeting BLyS/APRIL inhibitors for the treatment of AIDs. However, due to the scattered knowledge on the relationship between BLyS/APRIL and AIDs, it is necessary to sort out the existing data. Therefore, in this review, we describe the basic biological characteristics and functions of BLyS/APRIL in AIDs, summarize the potential clinical applications of related inhibitors, especially monoclonal antibodies and recombinant fusion proteins targeting BLyS/APRIL in AIDs, and also outline promising research directions.