Aberrant glycosylation of IgA1 and anti-glycan antibodies in IgA nephropathy: role of mucosal immune system.

Abstract

IgA nephropathy (IgAN), the most common glomerulonephritis, is characterized by mesangial IgA1-containing immunodeposits, proliferation of mesangial cells, and matrix expansion. Clinical onset is frequently heralded by synpharyngitic hematuria, macroscopic hematuria during an upper-respiratory tract infection. Clinical and laboratory data support a postulated extrarenal origin of the glomerular IgA1, likely derived from circulating immune complexes containing polymeric IgA1, deficient in galactose in the hinge-region O-glycans, bound by antiglycan antibodies. This aberrant IgA1 is produced by IgA1-secreting cells with abnormal activities of specific glycosyltransferases. The galactose deficiency affects IgA1 induced by mucosal antigens and elevated circulating levels of this abnormal IgA1 are hereditable, suggesting interactions of genetic and environmental factors. An abnormal mucosal immune response resulting in production of galactose-deficient IgA1 in IgAN patients is supported by several observations: the aberrant glycosylation affects mostly polymeric IgA1 produced by mucosal-associated IgA1-secreting cells (including those from tonsils), the synpharyngitic nature of the macroscopic hematuria, and the association of disease severity with polymorphisms of a pattern-recognition receptor, TLR9. Thus, IgAN is an auto-immune disease, induced by mesangial deposition of circulating complexes containing galactose-deficient IgA1. The aberrant glycosylation of IgA1 may reflect abnormal mucosal immune responses to infections of the upper respiratory tract in genetically predisposed individuals.

• Authors: Jan Novak, Zina Moldoveanu, Bruce A Julian, Milan Raska, Robert J Wyatt, Yusuke Suzuki, Yasuhiko Tomino, Ali G Gharavi, Jiri Mestecky, Hitoshi Suzuki
• Journal: Advances in oto-rhino-laryngology (Adv Otorhinolaryngol) Vol. 72 Pg. 60-3 ( 2011) ISSN: 1662-2847 [Electronic] Switzerland
• PMID: 21865691 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2011 S. Karger AG, Basel.

Chemical References

• Antibodies, Anti-Idiotypic
• Antigen-Antibody Complex
• Immunoglobulin A
• Polysaccharides

Topics

• Antibodies, Anti-Idiotypic (immunology, metabolism)
• Antigen-Antibody Complex (immunology)
• Glomerular Mesangium (immunology, metabolism)
• Glomerulonephritis, IGA (immunology, metabolism)
• Glycosylation
• Humans
• Immunity, Mucosal (physiology)
• Immunoglobulin A (immunology, metabolism)
• Mesangial Cells (immunology, metabolism)
• Mucous Membrane (immunology, metabolism)
• Polysaccharides (immunology)