VOMITOXIN (DEOXYNIVALENOL)-INDUCED IGA NEPHROPATHY IN THE B6C3F1 MOUSE - DOSE-RESPONSE AND MALE PREDILECTION

Oral exposure to the trichothecene vomitoxin (VT or deoxynivalenol) in mice induces marked elevation of total and autoreactive IgA, IgA immune complexes, and mesangial IgA deposition in a manner that is highly analogous to human IgA nephropathy. In this study, immunopathologic markers indicative of IgA nephropathy were compared in male and female B6C3F1 mice fed semipurified AIN-76A diet containing 0, 2, 10 or 25 ppm VT for 12 weeks. Males fed 10 and 25 ppm VT and females fed 25 ppm VT had increased serum IgA at 4 weeks. At week 8, male mice fed the minimal dose of 2 ppm VT and female mice fed 10 ppm also exhibited elevated serum IgA. IgA levels were consistently higher in treatment males than females with significant differences being observed in the 10-ppm dose group at 4 and 12 weeks. IgA coproantibodies were marginally increased (maximum of 2-fold) in mice of both genders fed 10 and 25 VT. At 8 and 12 weeks, serum IgM was depressed in male and female mice eating 10 and 25 ppm VT, whereas consistent effects on serum IgG or IgE were not observed. In similar fashion, male mice in the 2, 10 and 25 ppm VT groups exhibited microscopic hematuria as early as 4 weeks, whereas this occurred in females fed 10 and 25 ppm VT only at week 10 with urinary erythrocyte counts being lower than male counterparts. Mesangial deposition of IgA and C-3 was significantly increased in males exposed to 2, 10 and 25 ppm VT and in females exposed to 10 and 25 ppm VT, with males exhibiting a greater deposition than corresponding females. Based on these immunological parameters, males appeared more susceptible than female mice to VT-induced IgA dysregulation and IgA nephropathy in terms of latency, threshold dose, and severity.