APRIL (A Proliferation-Inducing Ligand, TNFSF13)

Class

Anti-APRIL monoclonal antibody

Pathway

B-cell/plasma-cell galactose-deficient IgA1 (Gd-IgA1) production in IgA nephropathy

APRIL (A Proliferation-Inducing Ligand, also called TNFSF13) is a signaling protein belonging to the tumor necrosis factor (TNF) superfamily. It is produced by immune and epithelial cells and acts on B lymphocytes and plasma cells by binding two receptors, TACI and BCMA, to promote cell survival and antibody production, particularly immunoglobulin A (IgA). This axis is central to mucosal immunity but becomes pathogenic in IgA nephropathy, a kidney disease in which B cells and plasma cells overproduce a poorly glycosylated form of IgA called galactose-deficient IgA1 (Gd-IgA1). This abnormal antibody forms immune complexes that deposit in the kidney's filtering units, triggering inflammation and progressive damage. Because APRIL helps sustain the B cells and plasma cells responsible for generating Gd-IgA1, neutralizing it with a monoclonal antibody is intended to reduce the supply of this harmful antibody at its source, rather than only treating downstream inflammation or blood pressure effects. This upstream approach reflects a broader rationale in autoimmune and antibody-mediated kidney diseases: intercepting the signals that sustain pathogenic antibody-producing cells can, in principle, limit ongoing tissue injury more durably than symptomatic management alone.