title: Pathogenesis of IgA nephropathy.
abstract: Since its first description in 1968, IgA nephropathy has remained the most common form of idiopathic glomerulonephritis leading to chronic kidney disease in developed countries. The exact pathogenesis of IgA nephropathy is still not well defined. Current data implicate an important genetic factor, especially in promoting the overproduction of an aberrant form of IgA1. The immunochemical aberrancy of IgA nephropathy is characterized by the undergalactosylation of O-glycans in the hinge region of IgA1. However, such aberrant glycosylation alone does not cause renal injury. The next stage of disease development requires the formation of glycan-specific IgG and IgA antibodies that recognize the undergalactosylated IgA1 molecule. These antibodies often have reactivity against antigens from extrinsic microorganisms and might arise from recurrent mucosal infection. B cells that respond to mucosal infections, particularly tonsillitis, might produce the nephritogenic IgA1 molecule. With increased immune-complex formation and decreased clearance owing to reduced uptake by the liver, IgA1 binds to the glomerular mesangium via an as yet unidentified receptor. Glomerular IgA1 deposits trigger the local production of cytokines and growth factors, leading to the activation of mesangial cells and the complement system. Emerging data suggest that mesangial-derived mediators following glomerular deposition of IgA1 lead to podocyte and tubulointerstitial injury via mesangio-podocytic-tubular crosstalk. This Review summarizes the latest findings in the pathogenesis of IgA nephropathy.
authors.affiliation: Nephrology Center, 10th floor, Li Shu Pui Block, Hong Kong Sanatorium and Hospital, 2 Village Road, Happy Valley, Hong Kong. knlai@hkucc.hku.hk
authors.forename: Kar Neng
authors.initials: KN
authors.lastname: Lai
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007678:Kidney Glomerulus / Q000503:physiopathology; D050527:Mesangial Cells / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A