Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/15201
Title: The pathogenic role of IgA1 O-linked glycosylation in the pathogenesis of IgA nephropathy.
Authors: Barratt, J
Smith, AC
Feehally, J
First Published: Jun-2007
Citation: NEPHROLOGY (CARLTON), 2007, 12 (3), pp. 275-284
Abstract: Numerous abnormalities of the IgA immune system have been reported in IgAN but the most consistent finding remains aberrant IgA1 O-linked glycosylation of the IgA1 hinge region. The defect comprises reduced galactosylation of O-linked N-acetylgalactosamine residues with or without changes in the terminal sialylation of the O-linked sugars. Aberrant O-galactosylation has been found in serum IgA1, in IgA1 isolated from tonsillar lymphocytes, and in IgA1 eluted from mesangial deposits. There is evidence that changes in IgA1 O-galactosylation lead to IgA immune complex formation and mesangial IgA deposition. Mesangial cells exposed to these IgA immune complexes proliferate and adopt a pro-inflammatory phenotype; they secrete cytokines, chemokines, growth factors and extracellular matrix components promoting glomerular inflammation and glomerulosclerosis. Recent evidence suggests that the control of IgA1 O-glycosylation is linked to class switching from IgD to IgA1 synthesis and that the pattern of IgA1 O-glycosylation may be programmed at the time of initial antigen encounter. IgA1 glycosylation varies between systemic and mucosal sites and the association of aberrant IgA1 galactosylation with low affinity, polymeric IgA1 antibodies against mucosal antigens suggests undergalactosylated IgA1 may in fact be a mucosal glycoform of IgA1. Although suited to the mucosal compartment, when these IgA1 glycoforms enter the systemic circulation in appreciable quantities they deposit in the mesangium and trigger glomerular inflammation. This review will discuss the evidence for the role of IgA1 O-glycosylation in the pathogenesis of IgAN and propose an explanation for the presence of aberrantly O-glycosylated IgA1 in the circulation of patients with IgAN.
DOI Link: 10.1111/j.1440-1797.2007.00797.x
ISSN: 1320-5358
Links: http://hdl.handle.net/2381/15201
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

Files in This Item:
There are no files associated with this item.


Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.