Authors of a review examined the growing evidence that autoantibodies may contribute to the pathogenesis of IgA nephropathy (IgAN). The best-established are IgG autoantibodies directed against galactose-deficient IgA1 (Gd-IgA1), which form immune complexes that deposit in the glomeruli and trigger inflammation. Researchers have also identified autoantibodies targeting endothelial cells, glomerular components, collagen, and mesangial cells, suggesting that IgAN may involve a broader spectrum of autoimmune activity than previously recognized.
More recent research has identified IgA autoantibodies against the mesangial-cell antigens β2-spectrin and CBX3. Approximately half of patients with IgAN in two cohorts had antibodies against one or both targets, and these antibodies showed characteristics of Gd-IgA1, potentially helping explain why some Gd-IgA1–containing immune complexes localize to the mesangium. However, direct evidence that these antibodies drive IgAN remains lacking. The authors conclude that clarifying their role could deepen understanding of disease mechanisms and potentially inform future biomarkers and therapeutic strategies.
Reference: Nihei Y, Suzuki Y. Autoimmunity in IgA nephropathy. Front Immunol. 2026 Mar 9;17:1782872. doi: 10.3389/fimmu.2026.1782872.
