Genetics and Immunopathogenesis of IgA Nephropathy

IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The hallmark of IgAN is underglycosylation in the hinge region of IgA1. Increasing evidence supports the underglycosylated IgA-containing immune-complex including IgG antibodies against the glycans of the hinge region of IgA1 are key factors for mesangial deposition and then trigger inflammation and glomerular injury. The polymeric IgA is produced after aberrant mucosal IgA response. The displacement of mucosal B cells to systemic lymphoid organs and bone marrow may arise from abnormal trafficking of lymphocytes along the mucosa–bone marrow axis involving changes of chemokines and adhesion molecules. This review will summarize the works on the genetics, the mucosal and systemic IgA immune response, mechanism of underglycosylation of IgA1, and the pathological effect of mesangial IgA deposition in IgAN.

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