L. Rasooly et Jj. Pestka, POLYCLONAL AUTOREACTIVE IGA INCREASE AND MESANGIAL DEPOSITION DURING VOMITOXIN-INDUCED IGA NEPHROPATHY IN THE BALB C MOUSE/, Food and chemical toxicology, 32(4), 1994, pp. 329
To establish the relationship between autoreactive antibodies and vomi
toxin-induced immunoglobulin A (IgA) nephropathy, the effects of dieta
ry vomitoxin exposure on the antigen specificity of serum IgA, IgA-pro
ducing cells and accumulated mesangial IgA in BALB/c mice were assesse
d. Exposure to dietary vomitoxin for 8 wk caused a significant increas
e in total serum IgA. There was a concurrent significant increase in s
erum IgA specific for trinitrophenol (TNP), phosphorylcholine, cardiol
ipin and sphingomyelin compared with controls, suggesting an elevation
of autoreactive IgA. Casein, a protein found in the AIN-76A diet, cou
ld inhibit binding of serum IgA to sphingomyelin and cardiolipin, indi
cating that these antibodies may be polyspecific. When enzyme-linked i
mmunospot assay was used to monitor autoreactive IgA production, trend
s 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 depo
sition of mesangial IgA was also observed in vomitoxin-fed mice compar
ed with controls. When IgA was eluted from the kidney sections of trea
ted mice and tested by enzyme-linked immunosorbent assay, it exhibited
a strong binding to the above antigen panel as well as inulin, DNA an
d casein. These data suggest that dietary vomitoxin induced the polycl
onal activation of IgA-producing cells and that resultant autoreactive
IgA was subsequently deposited in the kidney mesangium.