Polyclonal autoreactive IgA increase and mesangial deposition during vomitoxin-induced IgA nephropathy in the BALB/c mouse.
To establish the relationship between autoreactive antibodies and vomitoxin-induced immunoglobulin A (IgA) nephropathy, the effects of dietary vomitoxin exposure on the antigen specificity of serum IgA, IgA-producing cells and accumulated mesangial IgA in BALB/c mice were assessed. Exposure to dietary vomitoxin for 8 wk caused a significant increase in total serum IgA. There was a concurrent significant increase in serum IgA specific for trinitrophenol (TNP), phosphorylcholine, cardiolipin and sphingomyelin compared with controls, suggesting an elevation of autoreactive IgA. Casein, a protein found in the AIN-76A diet, could inhibit binding of serum IgA to sphingomyelin and cardiolipin, indicating that these antibodies may be polyspecific. When enzyme-linked immunospot assay was used to monitor autoreactive IgA production, trends were observed towards increased IgA-secreting cells specific for TNP, cardiolipin and sphingomyelin in Peyer's patches from vomitoxin-fed mice compared with control mice. IgA-producing cells reactive with TNP were increased in the spleen of vomitoxin-fed mice whereas effects on IgA-secreting cells for the other antigens were marginal. Marked deposition of mesangial IgA was also observed in vomitoxin-fed mice compared with controls. When IgA was eluted from the kidney sections of treated mice and tested by enzyme-linked immunosorbent assay, it exhibited a strong binding to the above antigen panel as well as inulin, DNA and casein. These data suggest that dietary vomitoxin induced the polyclonal activation of IgA-producing cells and that resultant autoreactive IgA was subsequently deposited in the kidney mesangium.
Rasooly
L
L
Department of Microbiology and Public Health, Michigan State University, East Lansing 48824.
Pestka
J J
JJ
D000818:Animals; D000918:Antibody Specificity; D001324:Autoantigens / Q000276:immunology; D002308:Cardiolipins / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000276:immunology*; D005922:Glomerulonephritis, IGA / Q000139:chemically induced* / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010767:Phosphorylcholine / Q000276:immunology; D010851:Picrates / Q000276:immunology; D013109:Sphingomyelins / Q000276:immunology
D001324:Autoantigens; D002308:Cardiolipins; D007070:Immunoglobulin A; D010851:Picrates; D013109:Sphingomyelins; D010767:Phosphorylcholine; C005858:picric acid