Experimental poststreptococcal glomerulonephritis elicited by IgG Fc‐binding M family proteins and blocked by IgG Fc fragment
Abstract:Burova L, Pigarevsky P, Seliverstova V, Gupalova T, Schalén C, Totolian A. Experimental poststreptococcal glomerulonephritis elicited by IgG Fc‐binding M family proteins and blocked by IgG Fc fragment. APMIS 2012; 120: 221–30.
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.
Document Type: Research Article
Publication date: March 1, 2012