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

Burova, Larissa ; Pigarevsky, Peter ; Duplik, Nadezhda ; Snegova, Vlada ; Suvorov, Alexander ; Schalén, Claës LU orcid and Totolian, Artem (2013) In Journal of Medical Microbiology 63. p.1272-1280
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... (More)
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. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medical Microbiology
volume
63
pages
1272 - 1280
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000326304700002
  • scopus:84881592300
  • pmid:23788594
ISSN
0022-2615
DOI
10.1099/jmm.0.059196-0
language
English
LU publication?
yes
id
89c235a5-4035-4dae-a293-bf798fefa492 (old id 4212382)
date added to LUP
2016-04-01 14:58:18
date last changed
2023-01-04 07:44:55
@article{89c235a5-4035-4dae-a293-bf798fefa492,
  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-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.}},
  author       = {{Burova, Larissa and Pigarevsky, Peter and Duplik, Nadezhda and Snegova, Vlada and Suvorov, Alexander and Schalén, Claës and Totolian, Artem}},
  issn         = {{0022-2615}},
  language     = {{eng}},
  pages        = {{1272--1280}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Journal of Medical Microbiology}},
  title        = {{Immune complex binding Streptococcus pyogenes type M12/emm12 in experimental glomerulonephritis}},
  url          = {{http://dx.doi.org/10.1099/jmm.0.059196-0}},
  doi          = {{10.1099/jmm.0.059196-0}},
  volume       = {{63}},
  year         = {{2013}},
}