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Nephrol Dial Transplant. 2002 Dec;17(12):2108-16.

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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1
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Abstract

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.

PMID:
12454220
[Indexed for MEDLINE]
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