2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2006060658v1 17/12/3520    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smith, A. C. Articles by Barratt, J. Search for Related Content PubMed PubMed Citation Articles by Smith, A. C. Articles by Barratt, J. Related Collections Related Article

O-Glycosylation of Serum IgA1 Antibodies against Mucosal and Systemic Antigens in IgA Nephropathy

University of Leicester Department of Infection, Immunity and Inflammation, and John Walls Renal Unit, Leicester General Hospital, Leicester, United Kingdom

Address correspondence to: Dr. Alice C. Smith, John Walls Renal Unit, Leicester General Hospital, Leicester LE4 5PW, UK. Phone: +44-116-258-8039; Fax: +44-116-258-4764; E-mail: aa50{at}le.ac.uk

Received for publication June 26, 2006. Accepted for publication August 29, 2006.

In IgA nephropathy (IgAN), serum IgA1 with abnormal O-glycosylation deposits in the glomerular mesangium. The underlying mechanism of this IgA1 O-glycosylation abnormality is poorly understood, but recent evidence argues against a generic defect in B cell glycosyltransferases, suggesting that only a subpopulation of IgA1-committed B cells are affected. For investigation of whether the site of antigen encounter influences IgA1 O-glycosylation, the O-glycosylation of serum IgA1 antibodies against a systemic antigen, tetanus toxoid (TT), and a mucosal antigen, Helicobacter pylori (HP), was studied in patients with IgAN and control subjects. Serum IgA1 was purified from cohorts of patients with IgAN and control subjects with HP infection and after systemic TT immunization. The IgA1 samples were applied to HP- and TT-coated immunoplates to immobilize specific antibodies, and IgA1 O-glycosylation profiles were assessed by binding of the O-glycan–specific lectin Vicia villosa using a modified ELISA technique. Although total serum IgA1 had raised lectin binding in IgAN, the O-glycosylation of the specific IgA1 antibodies to TT and HP did not differ between patients and control subjects. In both groups, IgA1 anti-HP had higher lectin binding than IgA1 anti-TT. This study demonstrates that IgA1 O-glycosylation normally varies in different immune responses and that patients produce the full spectrum of IgA1 O-glycoforms. IgA1 with high lectin binding was produced in response to mucosal HP infection in all subjects. The raised circulating level of this type of IgA1 in IgAN is likely to be a consequence of abnormal systemic responses to mucosally encountered antigens rather than a fundamental defect in B cell O-glycosylation pathways.

Related Article

This Month’s Highlights
J. Am. Soc. Nephrol. 2006 17: 3265-3266. [Full Text] [PDF]

This article has been cited by other articles:

				A. Smith, K. Molyneux, J. Feehally, and J. Barratt Is sialylation of IgA the agent provocateur of IgA nephropathy? Nephrol. Dial. Transplant., July 1, 2008; 23(7): 2176 - 2178. [Full Text] [PDF]

				W. Qin, X. Zhong, J. M. Fan, Y. J. Zhang, X. R. Liu, and X. Y. Ma External suppression causes the low expression of the Cosmc gene in IgA nephropathy Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1608 - 1614. [Abstract] [Full Text] [PDF]

				B. D. Oortwijn, M. P. Rastaldi, A. Roos, D. Mattinzoli, M. R. Daha, and C. van Kooten Demonstration of secretory IgA in kidneys of patients with IgA nephropathy Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3191 - 3195. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673