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Induction of Auto-Antibodies Against β(2) -Glycoprotein I in Mice by Protein H of Streptococcus Pyogenes.

van Os, G M A; Meijers, J C M; Ağar, C; Valls Serón, M; Marquart, J A; Åkesson, Per LU ; Urbanus, R T; Derksen, R H W M; Herwald, Heiko LU and Mörgelin, Matthias LU , et al. (2011) In Journal of Thrombosis and Haemostasis 9(12). p.2447-2456
Abstract
Background: The antiphospholipid syndrome (APS) is characterized by the persistent presence of auto-antibodies against β(2) -Glycoprotein I (β(2) -GPI). β(2) -GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish-hook shape after binding to phospholipids. Only the latter conformation is recognized by patient antibodies. β(2) -GPI has been shown to interact with Streptococcus pyogenes. Objective: Here we evaluated the potential of S. pyogenes derived proteins to induce auto-antibodies against β(2) -GPI. Methods and results: Four S. pyogenes surface proteins (M1 protein, protein H, SclA and SclB) were found to interact with β(2) -GPI. Only binding to protein H induces a conformational change in β(2)... (More)
Background: The antiphospholipid syndrome (APS) is characterized by the persistent presence of auto-antibodies against β(2) -Glycoprotein I (β(2) -GPI). β(2) -GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish-hook shape after binding to phospholipids. Only the latter conformation is recognized by patient antibodies. β(2) -GPI has been shown to interact with Streptococcus pyogenes. Objective: Here we evaluated the potential of S. pyogenes derived proteins to induce auto-antibodies against β(2) -GPI. Methods and results: Four S. pyogenes surface proteins (M1 protein, protein H, SclA and SclB) were found to interact with β(2) -GPI. Only binding to protein H induces a conformational change in β(2) -GPI, thereby exposing a cryptic epitope for APS-related auto-antibodies. Mice were injected with the four proteins. Only mice injected with protein H developed antibodies against the patient antibody related epitope in domain I of β(2) -GPI. Patients with pharyngotonsillitis caused by S. pyogenes who developed antibodies towards protein H also generated anti-β(2) -GPI antibodies. Conclusion: Our study demonstrated that a bacterial protein can induce a conformational change in β(2) -GPI resulting in the formation of auto-antibodies against β(2) -GPI. This constitutes a novel mechanism for the formation of auto-antibodies against β(2) -GPI. (Less)
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Contribution to journal
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published
subject
keywords
antiphospholipid syndrome, autoantibodies, ss 2-glycoprotein I
in
Journal of Thrombosis and Haemostasis
volume
9
issue
12
pages
2447 - 2456
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000298059500015
  • pmid:21985124
  • scopus:82755189081
ISSN
1538-7933
DOI
10.1111/j.1538-7836.2011.04532.x
language
English
LU publication?
yes
id
7fff5ca8-8641-480b-9a4e-9161bd66b115 (old id 2200668)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21985124?dopt=Abstract
date added to LUP
2011-11-02 09:37:26
date last changed
2017-11-05 03:11:53
@article{7fff5ca8-8641-480b-9a4e-9161bd66b115,
  abstract     = {Background: The antiphospholipid syndrome (APS) is characterized by the persistent presence of auto-antibodies against β(2) -Glycoprotein I (β(2) -GPI). β(2) -GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish-hook shape after binding to phospholipids. Only the latter conformation is recognized by patient antibodies. β(2) -GPI has been shown to interact with Streptococcus pyogenes. Objective: Here we evaluated the potential of S. pyogenes derived proteins to induce auto-antibodies against β(2) -GPI. Methods and results: Four S. pyogenes surface proteins (M1 protein, protein H, SclA and SclB) were found to interact with β(2) -GPI. Only binding to protein H induces a conformational change in β(2) -GPI, thereby exposing a cryptic epitope for APS-related auto-antibodies. Mice were injected with the four proteins. Only mice injected with protein H developed antibodies against the patient antibody related epitope in domain I of β(2) -GPI. Patients with pharyngotonsillitis caused by S. pyogenes who developed antibodies towards protein H also generated anti-β(2) -GPI antibodies. Conclusion: Our study demonstrated that a bacterial protein can induce a conformational change in β(2) -GPI resulting in the formation of auto-antibodies against β(2) -GPI. This constitutes a novel mechanism for the formation of auto-antibodies against β(2) -GPI.},
  author       = {van Os, G M A and Meijers, J C M and Ağar, C and Valls Serón, M and Marquart, J A and Åkesson, Per and Urbanus, R T and Derksen, R H W M and Herwald, Heiko and Mörgelin, Matthias and de Groot, P G},
  issn         = {1538-7933},
  keyword      = {antiphospholipid syndrome,autoantibodies,ss 2-glycoprotein I},
  language     = {eng},
  number       = {12},
  pages        = {2447--2456},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Journal of Thrombosis and Haemostasis},
  title        = {Induction of Auto-Antibodies Against β(2) -Glycoprotein I in Mice by Protein H of Streptococcus Pyogenes.},
  url          = {http://dx.doi.org/10.1111/j.1538-7836.2011.04532.x},
  volume       = {9},
  year         = {2011},
}