Persistent Dysregulation of IgA Production and IgA Nephropathy in the B6C3F1 Mouse Following Withdrawal of Dietary Vomitoxin (Deoxynivalenol)

To assess whether vomitoxin-induced dysregulation of IgA productionand IgA nephropathy are reversible, relevant immunologic parameterswere compared among experimental groups of B6C3F1 mice thatwere fed: (1) 25 ppm vomitoxin in AIN-76A semipurified dietfor 24 weeks (treatment group), (2) 25 ppm vomitoxin for 8 weeksand then control diet for 16 weeks (withdrawal group), and (3)control diet for 24 weeks (control group). Levels of serum IgAand microhematuria index in the treatment group were elevatedafter 4 to 8 weeks and continued to increase with further vomitoxinexposure. IgA immune complexes and mesangial IgA deposition,as quantitated by interactive laser cytometer image analysis,were also increased with toxin exposure at Weeks 8, 16, and24, whereas IgM, IgG, and complement component C3 depositionwere unaffected or depressed. Serum IgA, microhematuria index,and mesangial IgA deposition in withdrawal mice remained elevatedover those of the controls at Weeks 16 and 24 but were lessthan those of the treatment group. Cell recovery from Peyer'spatches (PP) as well as the percentages of IgA⁺ and CD4⁺ cellsin PP and spleen at Weeks 16 and 24 were greater in treatmentmice than in controls, but only the percentage of IgA⁺ cellsin PP was elevated in the withdrawal mice at these the sametime points. When IgA secretion by unstimulated and LPS-stimulatedsplenic lymphocytes was used as the measure of systemic production,it was elevated in both treatment and withdrawal mice at Weeks16 and 24. The results indicated that experimental dysregulationof IgA production and IgA nephropathy persisted up to 4 monthsafter a discrete period of dietary vomitoxin exposure, but thatthe severity of these effects did not increase in a progressivefashion.