The pathogenesis of acute poststreptococcal
glomerulonephritis (APSGN), a major nonsuppurative complication of group A streptococcal (GAS) throat or
skin disease, remains unclear. During the years, various theories based on certain streptococcal extracellular factors, as well as immunological mimicry between streptococci and renal tissue, have been forwarded. We earlier reported that many clinical GAS isolates with documented nephritogenic capacity show non-immune binding of monomeric or aggregated
IgG. Moreover, in a rabbit model of APSGN we obtained evidence for an important role of streptococcal
IgG Fc
binding proteins (IgGFcBPs) belonging to the M family
surface proteins; thus, hyperimmunization by whole IgGFcBP-positive streptococci was shown to induce renal glomerular changes with deposition of
IgG and
complement C3, resembling the picture recorded in human APSGN. These typical renal changes were always preceded by the appearance of circulating
anti-IgG antibodies. In the present work, using the same rabbit model, each of two purified IgGFcBPs, isolated from type M22 GAS, were found to elicit glomerular degenerative damage comparable to that caused by whole bacteria, as well as formation of
anti-IgG. In addition, the induction by whole streptococci (type M1) of experimental APSGN was inhibited by the i.v. administration of purified human or rabbit
IgG Fc, but not
Fab, fragment, supporting the importance of Fc-mediated mechanisms in causation of
glomerulonephritis. We propose that
anti-IgG antibody, induced by streptococcal IgGFcBP, facilitated renal accumulation of
IgG-containing complexes, which in turn triggered
complement deposition and proinflammatory cascades. Further studies on the possible beneficial effect of
IgG Fc fragment in APSGN should be of interest.