Quantitative assessment of mesangial immunoglobulin A (IgA) accumulation, elevated circulating IgA immune complexes, and hematuria during vomitoxin-induced IgA nephropathy.
Extended dietary exposure to the trichothecene vomitoxin (deoxynivalenol), a naturally occurring fungal contaminant of cereal grains, induces elevated serum IgA and mesangial IgA accumulation in a manner similar to the human glomerulonephritis, IgA nephropathy. A 12-week feeding study was conducted in the B6C3F1 mouse to evaluate the effects of exposure to 25 ppm dietary vomitoxin over time on formation of IgA immune complexes (IgA-IC), hematuria, and mesangial deposition of IgA, IgG, IgM, and complement component C3. Both serum IgA and IgA-IC were significantly elevated in vomitoxin-exposed treatment groups compared to controls at weeks 4, 8, and 12, whereas serum IgG was unaffected. The incidence of hematuria was also significant in vomitoxin-exposed mice at weeks 4, 8, and 12. Quantitative immunofluorescence intensity measurements using interactive laser cytometer image analysis revealed significantly greater mesangial IgA accumulation in vomitoxin-fed mice compared to controls at weeks 4, 8, and 12. Although glomerular IgG and IgM deposition was present in both controls and treated mice, it was significantly lower in treated mice as compared to controls at week 12. Mesangial C3 deposition was not induced by vomitoxin feeding. Elevated IgA-IC, hematuria, and IgA mesangial accumulation occurring during exposure to vomitoxin mimicked human IgA nephropathy, whereas the absence of mesangial C3 represented a major difference between this toxin-induced immune dysregulation and the human disease.
Dong
W
W
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824.
Sell
J E
JE
Pestka
J J
JJ
D000818:Animals; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005920:Glomerular Mesangium / Q000276:immunology*; D005922:Glomerulonephritis, IGA / Q000139:chemically induced / Q000276:immunology*; D006417:Hematuria / Q000276:immunology*; D007105:Immune Complex Diseases / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D014255:Trichothecenes / Q000633:toxicity*
D007070:Immunoglobulin A; D014255:Trichothecenes; D016650:Fluorescein-5-isothiocyanate; C007262:deoxynivalenol