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

Nephrol Dial Transplant. 2002 Dec;17(12):2108-16. doi: 10.1093/ndt/17.12.2108.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood / metabolism
  • Chemical Phenomena
  • Chemistry, Physical
  • Glycosylation
  • Hydrogen-Ion Concentration
  • Immunoglobulin A / chemistry
  • Immunoglobulin A / metabolism*
  • Interleukin-12 / pharmacology
  • Interleukin-12 / physiology*
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism*
  • Kidney Glomerulus / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Polymers


  • Immunoglobulin A
  • Polymers
  • Interleukin-12