Nephritogenic activity of IgA-binding streptococcus pyogenes : An experimental model of IgA glomerulonephritis

• The aim of present study was to arrange an experimental rabbit model for IgA-nephropathy. To this purpose, an approach was attempted which was previously successfully applied in rabbits, aiming for induction of post-streptococcal glomerulonephritis (PSGN). To induce the nephropathy, we used two Streptococcus pyogenes strains of M4 and M60 serotypes which showed differential IgA-binding capacity mediated by the IgAFc microbial receptors. The renal tissue damage was developed in most animals treated with emm60 S. pyogenes characterized by marked IgAFcR expression and higher IgA-binding ability. By means of morphometric analysis. Significant morphological and immunochemical 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 oedema; (ii) marked C3-complement deposition in proximal and distal tubules; (iii) a significant infiltration of cortical and medullar areas by lymphocytes associated with weak TNFα production. Noteworthy, we did not observe local IgG deposition in any cases, thus allowing to exclude any role of anti-IgG, or other IgG's in evolution of the pathology. Alternatively, the IgA-deposits may occur due to microbial IgA FcR-IgAcontaining cmplexes, as earlier shown by the Swedish scientists. The above tissue changes were completely absent in kidneys of control animals. 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Experimental model

IgA nephropathy

IgA-binding streptococci

Streptococcus pyogenes

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)