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Published on: June 29, 2016
Immune complex binding Streptococcus pyogenes type M12/emm12 in experimental glomerulonephritis
Larissa Burova1, Peter Pigarevsky1, Nadezhda Duplik1
1Institute of Experimental Medicine RAMS, St-Petersburg, Russia.
Abstract:
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-α 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.
Insights
Certain group A streptococci (GAS) strains bind immune complexes (ICs), leading to kidney inflammation and damage similar to post-streptococcal glomerulonephritis (PSGN). This binding is linked to the nephritogenic potential of M12/emm12 GAS strains.
Area of Science:
- Microbiology
- Immunology
- Nephrology
Background:
- Previous studies implicated streptococcal IgG Fc-binding proteins (IgGFcBP) in post-streptococcal glomerulonephritis (PSGN) pathogenesis.
- IgGFcBP can trigger anti-IgG production and enhance renal IgG/immune complex (IC) deposition, activating complement and cytokines.
Purpose of the Study:
- To investigate the role of immune complex (IC) binding by type M12/emm12 group A streptococci (GAS) in a rabbit model of PSGN.
- To determine if IC binding correlates with nephritogenic potential and specific pathological changes in the kidney.
Main Methods:
- Utilized a rabbit model and clinical isolates of type M12/emm12 GAS, including IC-binding and non-binding strains.
- Assessed glomerular changes, IgG and C3 deposition, and cytokine secretion (IL-6, TNF-α) in response to GAS infection.
- Measured anti-IgG antibody titers in response to different GAS strains.
Main Results:
- Type M12/emm12 GAS strains frequently bound artificial ICs (peroxidase-anti-peroxidase IgG or tetanus toxoid-anti-tetanus IgG) rather than monomeric IgG.
- Rabbits injected with IC-binding GAS isolates developed glomerular inflammation, membrane thickening, IgG/C3 deposition, and IL-6/TNF-α secretion, mimicking human PSGN.
- Non-binding strains did not induce renal changes, while IC-binding strains elevated anti-IgG titers.
Conclusions:
- Selective binding of ICs by type M12/emm12 GAS strains is crucial for their significant nephritogenic potential.
- This IC-binding mechanism contributes to the pathogenesis of PSGN, highlighting a key virulence factor in specific GAS types.
