Emerging role of monoclonal antibodies in the treatment of IgA nephropathy.

IgA nephropathy is the most common primary glomerulonephritis worldwide. Immune complexes, composed of galactose-deficient IgA1 and Gd-IgA1 autoantibodies, are deposited in the mesangial area of the glomeruli where they induce complement-mediated inflammation. This may result in the reduced kidney function, which can progress to end-stage kidney disease. Treatment options are very limited. Treatments which directly affect the formation of pathogenic Gd-IgA1 antibodies and anti-Gd-IgA1 antibody-containing immune complexes are needed. This article reviews potential therapies, namely monoclonal antibodies, that may affect the main axis of pathogenesis of IgA nephropathy with a discussion of their potential impact on the outcome of IgAN. PubMed was used to perform the literature search, which included papers on "treatment of IgA nephropathy"combined with "biological therapy", or 'monoclonal antibodies, atacicept, sibeprenlimab, rituximab, felzartamab, narsoplimab, iptacopan' published up to 2023. The new treatment options are aimed at the immunopathogenesis of IgAN, including depletion or modulation of Gd-IgA1 producing B cells, plasma cells, alternate or lectin pathway of complement. Monoclonal antibodies may target both B cells and T cells and also the factors needed for their activation and survival, e.g. BAFF or APRIL.