Induction of Auto-Antibodies Against β(2) -Glycoprotein I in Mice by Protein H of Streptococcus Pyogenes.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2200668
- author
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- antiphospholipid syndrome, autoantibodies, ss 2-glycoprotein I
- in
- Journal of Thrombosis and Haemostasis
- volume
- 9
- issue
- 12
- pages
- 2447 - 2456
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000298059500015
- pmid:21985124
- scopus:82755189081
- pmid:21985124
- 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
- 2016-04-01 10:25:58
- date last changed
- 2022-04-27 22:02:57
@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}}, keywords = {{antiphospholipid syndrome; autoantibodies; ss 2-glycoprotein I}}, language = {{eng}}, number = {{12}}, pages = {{2447--2456}}, publisher = {{Wiley-Blackwell}}, 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}}, doi = {{10.1111/j.1538-7836.2011.04532.x}}, volume = {{9}}, year = {{2011}}, }