Immune complex binding Streptococcus pyogenes type M12/emm12 in experimental glomerulonephritis

Summary, in English

In a rabbit model, we have previously reported evidence for a pathogenic role of streptococcal IgG Fc-binding proteins (IgGFcBP) in poststreptococcal glomerulonephritis (PSGN). These proteins, of the M protein family, were shown to trigger anti-IgG production and enhance renal deposition of IgG and/or immune complexes (ICs), with resulting activation of complement and cytokine cascades. In the present study, type M12/emm12, group A streptococci (GAS) were found often to bind artificial ICs, viz. peroxidase anti-peroxidase rabbit IgG (PAP) or tetanus toxoid-anti-tetanus human IgG (TAT), rather than monomeric IgG. Animals injected with each of four IC binding clinical isolates (from patients with scarlet fever or PSGN) showed pronounced inflammatory and degenerative glomerular changes, morphologically similar to human PSGN, with membrane thickening and IgG and complement C3 deposition, as well as secretion of IL-6 and TNF-alpha by mesangial and endothelial cells. In contrast, non-binding strains (two from asymptomatic carriers and one from a PSGN case) failed to trigger any renal changes. Only the IC binding strains induced elevated titres of anti-IgG. Though the streptococcal binding component(s) has not been demonstrated, the selective binding of ICs by type M12/emm12 strains appears important for the well-known, marked nephritogenic potential of this GAS type.

• Författare: Larissa Burova; Peter Pigarevsky; Nadezhda Duplik; Vlada Snegova; Alexander Suvorov; Claës Schalén; Artem Totolian
• Avdelning/ar: Avdelningen för medicinsk mikrobiologi
• Publiceringsår: 2013
• Språk: Engelska
• Sidor: 1272-1280
• Publikation/Tidskrift/Serie: Journal of Medical Microbiology
• Volym: 63
• Länkar: http://dx.doi.org/10.1099/jmm.0.059196-0
• Dokumenttyp: Artikel i tidskrift
• Förlag: Lippincott Williams & Wilkins
• Ämne: Microbiology in the medical area
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 0022-2615