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Antibodies against a surface protein of Streptococcus pyogenes promote a pathological inflammatory response.

Kahn, Fredrik LU ; Mörgelin, Matthias LU ; Shannon, Oonagh LU ; Norrby-Teglund, Anna; Herwald, Heiko LU ; Olin, Anders LU and Björck, Lars LU (2008) In PLoS Pathogens 4(9).
Abstract
Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein-induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP... (More)
Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein-induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein-fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Pathogens
volume
4
issue
9
publisher
Public Library of Science
external identifiers
  • wos:000259783300007
  • pmid:18787689
  • scopus:53049110308
ISSN
1553-7366
DOI
10.1371/journal.ppat.1000149
language
English
LU publication?
yes
id
12d22186-fa11-4def-8a9a-2b97cdef99e1 (old id 1243074)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18787689?dopt=Abstract
date added to LUP
2008-10-07 14:34:04
date last changed
2017-08-13 04:33:50
@article{12d22186-fa11-4def-8a9a-2b97cdef99e1,
  abstract     = {Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein-induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein-fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response.},
  articleno    = {e1000149},
  author       = {Kahn, Fredrik and Mörgelin, Matthias and Shannon, Oonagh and Norrby-Teglund, Anna and Herwald, Heiko and Olin, Anders and Björck, Lars},
  issn         = {1553-7366},
  language     = {eng},
  number       = {9},
  publisher    = {Public Library of Science},
  series       = {PLoS Pathogens},
  title        = {Antibodies against a surface protein of Streptococcus pyogenes promote a pathological inflammatory response.},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1000149},
  volume       = {4},
  year         = {2008},
}