Experimental IgA nephropathy induced by a low-dose environmental mycotoxin, nivalenol.
Based on the hypothesis that IgA nephropathy (IgAN) is triggered by some exogenous antigen(s) which induces dysregulation of the mucosal immune system, we developed an experimental model of orally induced IgAN by an environmental mycotoxin, nivalenol (NIV), which often contaminates agricultural products in Southeast Asia and Japan. In the present study, low doses of oral NIV reproducibly induced significant IgA deposits in the glomerular mesangium and elevated serum IgA levels in mice irrespective of the strain; the degree of immunopathological changes analogous to human IgAN was associated with the dose and duration of NIV treatment. Furthermore, a competitive enzyme-linked immunosorbent assay with an NIV analogue-protein conjugate disclosed that the IgA antibody in the sera from the NIV model mice had a higher affinity to the mycotoxin. Conclusively, these findings suggest that NIV induces some pathological changes in mice which resemble those in human IgAN, and that this mycotoxin is associated with pathogenesis in some types of glomerulonephritis.
Hinoshita
F
F
Kidney Center, Toranomon Hospital, Tokyo, Japan.
Suzuki
Y
Y
Yokoyama
K
K
Hara
S
S
Yamada
A
A
Ogura
Y
Y
Hashimoto
H
H
Tomura
S
S
Marumo
F
F
Ueno
Y
Y
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D005922:Glomerulonephritis, IGA / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008854:Microscopy, Electron; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*; D014255:Trichothecenes / Q000008:administration & dosage / Q000633:toxicity*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009183:Mycotoxins; D014255:Trichothecenes; C038405:nivalenol