Aberrant glycosylation of iga1 and anti-glycan antibodies in iga nephropathy: Role of mucosal immune system

Jan Novak, Zina Moldoveanu, Bruce A. Julian, Milan Raska, Robert J. Wyatt, Yusuke Suzuki, Yasuhiko Tomino, Ali G. Gharavi, Jiri Mestecky, Hitoshi Suzuki

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

43 Scopus citations


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.

Original languageEnglish
Title of host publicationRecent Advances in Tonsils and Mucosal Barriers of the Upper Airways
Subtitle of host publication7th International Symposium on Tonsils and Mucosal Barriers of the Upper Airways, Asahikawa, July 2010: Proceedings
EditorsYasuaki Harabuchi, Tatsuya Hayashi, Akihiro Katada
Number of pages4
StatePublished - Aug 2011
Externally publishedYes

Publication series

NameAdvances in Oto-Rhino-Laryngology
ISSN (Print)0065-3071


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