title: Structural features of IgA molecules which contribute to IgA nephropathy.
abstract: IgA nephropathy (IgAN) is characterised by the mesangial deposition of polymeric IgA1 (pIgA1). pIgA1 production is reduced in the mucosal immune system in IgAN and increased in the marrow; this switch may be secondary to a defect in gammadeltaT cell control of IgA production. However this does not explain the mechanism by which pIgA1 deposits in the mesangium. There is no direct evidence that classical immune complex deposition occurs in IgAN and alternative mechanisms resulting from physicochemical abnormalities of the IgA1 molecule, particular altered glycosylation, have been proposed. IgA1 has a distinctive hinge region which is a site for O-glycosylation. There is reduced terminal galactose on the hinge region O-glycans of circulating IgA1 in IgAN, perhaps due to a defect in B cell beta1,3 galactosyltransferase. A concomitant O-glycan defect in mesangial IgA1 has not yet been proven. Altered hinge O-glycosylation may have substantial impact on the quaternary structure of the IgA1 molecule influencing its capacity to interact with matrix proteins, IgA receptors on mesangial cells and leucocytes, and complement; it may therefore play a key role in the pathogenesis of mesangial deposition of IgA1 and subsequent glomerular injury in IgAN.
authors.affiliation: Department of Nephrology, Leicester General Hospital, UK. john@feehally.demon.co.uk
authors.forename: J
authors.initials: J
authors.lastname: Feehally
authors.forename: A C
authors.initials: AC
authors.lastname: Allen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D005920:Glomerular Mesangium / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000209:etiology*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000737:chemistry*; D037102:Lectins / Q000378:metabolism; D008969:Molecular Sequence Data
chemical_list: D007070:Immunoglobulin A; D037102:Lectins