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 immu ne complexes, and mesangial IgA deposition in a manner that is highly analogous to human IgA nephropathy. In this study, immunopathologic ma rkers indicative of IgA nephropathy were compared in male and female B 6C3F1 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 mini mal dose of 2 ppm VT and female mice fed 10 ppm also exhibited elevate d serum IgA. IgA levels were consistently higher in treatment males th an females with significant differences being observed in the 10-ppm d ose group at 4 and 12 weeks. IgA coproantibodies were marginally incre ased (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 V T 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 uri nary 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, wi th males exhibiting a greater deposition than corresponding females. B ased on these immunological parameters, males appeared more susceptibl e than female mice to VT-induced IgA dysregulation and IgA nephropathy in terms of latency, threshold dose, and severity.