The role of antibody glycosylation in autoimmune and alloimmune kidney diseases.

Immunoglobulin glycosylation is a pivotal mechanism that drives the diversification of antibody functions. The composition of the IgG glycome is influenced by environmental factors, genetic traits and inflammatory contexts. Differential IgG glycosylation has been shown to intricately modulate IgG effector functions and has a role in the initiation and progression of various diseases. Analysis of IgG glycosylation is therefore a promising tool for predicting disease severity. Several autoimmune and alloimmune disorders, including critical and potentially life-threatening conditions such as systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and antibody-mediated kidney graft rejection, are driven by immunoglobulin. In certain IgG-driven kidney diseases, including primary membranous nephropathy, IgA nephropathy and lupus nephritis, particular glycome characteristics can enhance in situ complement activation and the recruitment of innate immune cells, resulting in more severe kidney damage. Hypofucosylation, hypogalactosylation and hyposialylation are the most common IgG glycosylation traits identified in these diseases. Modulating IgG glycosylation could therefore be a promising therapeutic strategy for regulating the immune mechanisms that underlie IgG-driven kidney diseases and potentially reduce the burden of immunosuppressive drugs in affected patients.