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 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.