Journal Article

Interleukin‐12 alters the physicochemical characteristics of serum and glomerular IgA and modifies glycosylation in a ddY mouse strain having high IgA levels

Ikei Kobayashi, Fumiaki Nogaki, Hitoshi Kusano, Takahiko Ono, Shigeki Miyawaki, Haruyoshi Yoshida and Eri Muso

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 17, issue 12, pages 2108-2116
Published in print December 2002 | ISSN: 0931-0509
Published online December 2002 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/17.12.2108
Interleukin‐12 alters the physicochemical characteristics of serum and glomerular IgA and modifies glycosylation in a ddY mouse strain having high IgA levels

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Background. We recently developed a ddY mouse strain having high IgA levels (HIGA) that provided a murine model of IgA nephropathy. We additionally showed that administration of interleukin (IL)‐12, a potent helper T (Th)1‐inducing cytokine, induced an apparent reduction in serum IgA levels. In the present study, we assessed the influence of IL‐12 administration on several physicochemical characteristics of nephritogenic IgA molecules in HIGA mice.

Methods. HIGA mice received daily intraperitoneal injections of IL‐12 or control injections of phosphate‐buffered saline for 3 weeks. Crescent formation and levels of circulating and glomerular IgA were analysed. Moreover, potential changes in charge, size, and glycosylation of serum and glomerular IgA were investigated.

Results. In the IL‐12 group, glomerular IgA deposition was faint, although crescent formation was more marked than in the control group. Serum IgA levels in IL‐12 mice were significantly lower than in controls. IL‐12‐treated mice also showed markedly decreased acidic and polymeric IgA both in sera and in glomerular eluate. A lectin‐binding study revealed a markedly reduced ratio of sialylated and galactosylated IgA in the sera and in glomerular eluate from HIGA mice kidneys. IL‐12 treatment significantly increased sialylation and galactosylation of circulating IgA, although glycosylation of IgA in glomerular eluate remained low.

Conclusions. In HIGA mice showing under‐glycosylation, IL‐12 administration may lead to changes in the physicochemical characteristics of IgA, and this may occur through a shift to Th1. These results suggest that the Th1 and Th2 balance might play a role in the development of immunopathologic lesions in this model of IgA nephropathy.

Keywords: anionic charge; crescent formation; glycoprotein; helper T cell; IgA nephropathy; polymeric IgA

Journal Article.  4453 words.  Illustrated.

Subjects: Nephrology

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