Interleukin-12 alters the physicochemical characteristics of serum and glomerular IgA and modifies glycosylation in a ddY mouse strain having high IgA levels.
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.
Kobayashi
Ikei
I
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nogaki
Fumiaki
F
Kusano
Hitoshi
H
Ono
Takahiko
T
Miyawaki
Shigeki
S
Yoshida
Haruyoshi
H
Muso
Eri
E
D000818:Animals; D001769:Blood / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006031:Glycosylation; D006863:Hydrogen-Ion Concentration; D007070:Immunoglobulin A / Q000737:chemistry / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology / Q000502:physiology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D011108:Polymers
D007070:Immunoglobulin A; D011108:Polymers; D018664:Interleukin-12