Immuno-pathological studies in IgA nephropathy : The role of virus for etiological and progressive factors

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In order to produce an experimental model of IgA nephropathy, a histologiral and virological study of mice inoculated with a virus was carried out. First, mice were intravenously inoculated twice at an interval of 1-28 days purified with Cox.B4 virus. The kidneys were obtained from each mouse 36 hours after the second inoculation, and examined for histological changes such as mesangial deposits. Mesangial deposits were marked in mice given two inoculation at an interval of 14 days or more, indicating that antigen stimulations repeated at a sufficiently long interval are necessary for producing mesangial deposits. Another series of 4-week-old mice were inoculated with Cox.B4 virus 4-8 times at 4-week intervals either intravenously (i.v. group) or intraperitoneally (i.p. group). The kidneys were obtained from each mice one month after the final inoculation, and examined for histological changes. In the i.v. group, light microscopy revealed PAS- positive deposits in the mesangium after 4 … More inoculations. The deposits were more marked after 6 or more inoculations, accompanied by uneven hypertrophy of the loop wall and formation of crescents. By immunofluorescence, IgG was most deeply stained in speciments obtained after 4 or 5 inoculations, whereas IgA and IgG were stained to the same degree in some speciments after 6 or more inoculations. All speciments were positive for virus-Ag, the intensity of staining being increased in proportion to the number of inoculations. Electron microscopy disclosed deposits in subepithelial and subendothelial legions. In the i.p. group, light microscopy showed PAS-positive deposits in the mesangium after 4 or more inoculations. After 6 or more inoculations, there was uneven hypertrophy of the basement membrane, but no formation of crescents. By immunofluorescence, IgG, IgA and IgM were deeply stained in the mesangium in comparison with controls; IgA was always stained predominantly. Virus-Ag was positive in all speciments. Electron microscopic findings were similar to those in the i.v. group. It was thus demonstrated that intermittent intraperitoneal inoculation with Cox.B4 virus in mice produces renal lesions closely resembling those in human IgA nephropathy. Less