Targeting B cells in IgA nephropathy: from pathogenic insight to therapeutic horizon

IgA nephropathy (IgAN) remains the most common primary glomerulonephritis globally. Advances in mucosal immunology have illuminated the role of dysregulated B cell activity, galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-specific antibody formation, in driving disease pathogenesis. Therapeutic targeting of the mucosal immune system and, more specifically, B cell survival and differentiation pathways have entered late-stage development, offering a mechanistically guided approach to disease modification. Targeting of the gut associated lymphoid tissue (GALT) of the terminal ileum, BAFF and/or APRIL antagonists and CD38 targeted agents have all demonstrated efficacy in reducing proteinuria and preserving kidney function. Emerging cellular and bispecific platforms, although early in development, raise the prospect of deeper immunologic remodelling. Precision tools, such as Gd-IgA1 quantification, single-cell transcriptomics, and pharmacogenomics, are being explored to optimise treatment selection and duration. As real-world data and long-term safety outcomes accumulate, B cell–directed therapies are likely to become a commonly used treatment option in IgAN.