Nephrol Dial Transplant (2002) 17: 2108-2116
© 2002 European Renal Association-European Dialysis and Transplant Association
Interleukin-12 alters the physicochemical characteristics of serum and glomerular IgA and modifies glycosylation in a ddY mouse strain having high IgA levels
1 Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 2 Research Laboratories, Nippon Shinyaku Co. Ltd, Kyoto, 3 Department of Clinical Laboratory Medicine and Nephrology, Fukui Medical University, Fukui and 4 Division of Nephrology and Dialysis, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan
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
Correspondence and offprint requests to: Eri Muso, MD, PhD, Division of Nephrology and Dialysis, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, 2-4-20, Ohgimachi, Kita-ku, Osaka 530-8480, Japan. Email: muso{at}kitano-hp.or.jp
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