title: Primary IgA nephropathy: new insights into pathogenesis.
abstract: Since its first description more than 40 years ago, IgA nephropathy has become the most common pattern of primary glomerulonephritis identified in all areas of the world where renal biopsy is routinely performed. This review discusses advances in our understanding of the pathogenesis of IgA nephropathy, principally focusing on work published in the past 5 years. It has been recognized for some time that one of the most consistent features of IgA nephropathy is an alteration in the complement of serum IgA1 O-glycoforms, with an overrepresentation of poorly galactosylated IgA1 O-glycoforms both in the serum and mesangial deposits of patients with IgA nephropathy. New data suggest that poorly galactosylated IgA1 O-glycoforms might act either as autoantigens driving the formation of glycan-specific antibodies, or antigens for cross-reactive antimicrobial antibodies. Formation of these circulating and mesangial IgA-containing immune complexes appears pivotal to the pathogenesis of IgA nephropathy and there is strong in vitro data to support their role in activation of mesangial cells, induction of podocyte injury, and activation of proximal tubular epithelial cells. Genetic factors are likely to influence many facets of pathogenesis both in primary and familial IgA nephropathy, however, to date work in this area has failed to identify consistent candidate genes.
authors.affiliation: The John Walls Renal Unit, Leicester General Hospital and Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barratt
authors.forename: John
authors.initials: J
authors.lastname: Feehally
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007684:Kidney Tubules / Q000473:pathology; D050527:Mesangial Cells / Q000502:physiology; D050199:Podocytes / Q000473:pathology; D011961:Receptors, Fc / Q000378:metabolism; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D000936:Antigen-Antibody Complex; D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc; D051193:Toll-Like Receptors; D005690:Galactose