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Abstract
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.
Key Words
IgA nephropathy
Nivalenol
Experimental model
Mucosal immunity
Pathogenesis
Introduction
IgA nephropathy (IgAN) was first described by Berger and Hinglais [1] in 1968. Subsequently, potential pathogens which might induce IgAN have been experimentally and clinically studied [2-21]. Several viruses, some bacteria, food antigens and others have been included as etiologic candidates. Unfortunately, no particular pathogenic cause has been elucidated in human IgAN.
The following features are characteristic of IgAN: IgA is predominantly deposited in glomeruli with various grades of mesangial proliferation in every patient, and serum IgA levels are elevated in nearly half of IgAN patients [22]. It is also known that IgA-specific regulatory lymphocytes are well represented in the mucosal immune system, and IgA production is initiated primarily in this system. In light of these facts, we hypothesize that IgAN is triggered by some exogenous antigen(s) which induces dysregulation of the mucosal immune system, in agreement with the proposal of Emancipator et al. [4] and other researchers [23, 24].
Another remarkable feature of IgAN is that the apparent incidence of this disease varies greatly from country to country. The disease is particularly prevalent in southern Europe, Southeast Asia, and Australia [25, 26]. In Japan, IgAN is the most common form of glomerulonephritis, and the incidence of this disorder is about 30-40% in patients...