BACKGROUND. Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis, in which the diagnostic criterion is the deposit of immunoglobulin A of the IgA1 subclass in the mesangial cells of renal glomeruli. A significant place in the pathogenesis of IgAN belongs to GAS infections. The aim of this investigation was to arrange an experimental rabbit model to study of pathogenesis IgA-nephropathy.
MATERIAL AND METHODS. To induce in rabbits the IgAN we used two S.pyogenes strains of M4 and M60 serotypes, which showed differential IgA-binding capacity. After the end of injections of streptococci, the kidneys of the rabbits were subjected to immunohistological analysis.
RESULTS. The renal tissue damage was developed in most animals treated with S. pyogenes M60 characterized by higher IgA-binding ability. Significant morphological and immunohistological glomerular changes were revealed in 6/10 rabbits, as follows: (i) massive IgA deposition in the mesangial glomerular cells, atrophy of the capillary net, and tissue edema; (ii) marked C3-complement deposition in proximal and distal tubules; (iii) a significant infiltration of cortical and medullar areas by lymphocytes associated with TNFα production. We did not observe local IgG deposition in any cases, thus allowing excluding any role of IgG in evolution of the pathology. Alternatively, the IgA-deposits may occur due to microbial IgA FcR–IgA containing cоmplexes. The above tissue changes were completely absent in kidneys of control animals.
CONCLUSION. Taken together, these data suggest that we have developed an experimental model similar to IgA-nephropathy in humans. The results also extend our knowledge on pathogenic effects of the IgA Fc-binding proteins of Streptococcus pyogenes.