Autoimmune streptococcal glomerulonephritis: the problem of nephritogenicity of Streptococcus pyogenes

Abstract

Acute post-streptococcal glomerulonephritis usually occurs as a complication after a streptococcal infection due to untimely or inadequate antibiotic therapy. The etiology of post-streptococcal glomerulonephritis has been studied rather comprehensively. Today, both clinicians and microbiologists do not deny the dominant role of Streptococcus pyogenes (streptococcus attributed to serological group A, GAS). Usually, emergence of acute post-streptococcal glomerulonephritis (APSGN) is associated with the so-called GAS-related "nephritogenicity" often judged by appearance and accumulation of antibodies to the antigens and extracellular products of streptococcal cells in patient blood. This interpretation is quite loose and most likely evidence about a link to the bacterial strain, rather than its nephritogenicity. Many studies refer and still attribute a leading role of "nephritogenic" factors to various streptococcal antigens and related biologically active products. Streptococcal nephritogenic factors include cross-reacting antigens, streptokinase, cysteine proteinase, endostreptosin a GAS cell membrane protein as well as plasmin-tropic enzyme glyceraldehyde-3-phosphate dehydrogenase. Nephritogenicity of all such streptococcal products is suspected to result from the fact that they are found in renal biopsies like specific patient blood serum antibodies. Regarding a term of nephritogenicity, it has been evidenced that it cannot be attributed to any specific streptococcal cell product. This review attempted to analyze a number of bacterial products as starting factors triggering this process. APSGN can be reproduced experimentally in rabbits by intravenous administration of a heat-killed Streptococcus pyogenes culture. In our experiments, strains of serotypes 1, 4, 12, 15, 22 were used. They produced M-proteins and had the ability to bind human and rabbit immunoglobulin G by interacting with the Fc part of the IgG molecule. In numerous series of experiments, evidence was obtained regarding the initiating role of GAS IgGFc-receptor proteins in developing APSGN. Recent studies confirmed the role of streptococcal IgGFc-binding proteins in the initiation of glomerulonephritis after animals were inoculated with temperature-killed IgGFc-positive GAS. This approach excluded a large group of bacterial extracellular agents from the list of APSGN-initiating candidates. An unconventional view on the pathogenesis of GAS-infection-coupled complications may allow approaching their prevention or new treatment strategies.