Induction of anti- beta 2-glycoprotein I autoantibodies in mice by protein H of Streptococcus pyogenes

Background:The antiphospholipid syndrome (APS) is characterized by the persistent presence of anti- beta 2-glycoprotein I ( beta 2-GPI) autoantibodies. beta 2-GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish-hook conformation after binding to phospholi...

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Published in:Journal of thrombosis and haemostasis 2011-12, Vol.9 (12), p.2447-2456
Main Authors: VAN OS, GMA, MEIJERS, JCM, Agar, C, Seron, M V, Marquart, Ja, AaKESSON, P, Urbanus, R T, DERKSEN, RHWM, Herwald, H, MOeRGELIN, M, DE GROOT, PG
Format: Article
Language:English
Subjects:
antiphospholipid syndrome
Autoantibodies
Collagen
Epitopes
Pharyngotonsillitis
Phospholipids
protein B
protein H
Streptococcus pyogenes
Thrombosis
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Summary:Background:The antiphospholipid syndrome (APS) is characterized by the persistent presence of anti- beta 2-glycoprotein I ( beta 2-GPI) autoantibodies. beta 2-GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish-hook conformation after binding to phospholipids. Only the latter conformation is recognized by patient antibodies. beta 2-GPI has been shown to interact with Streptococcus pyogenes. Objective:To evaluate the potential of S. pyogenes-derived proteins to induce anti- beta 2-GPI autoantibodies. Methods and results:Four S.|>pyogenes surface proteins (M1 protein, protein H, streptococcal collagen-like protein A [SclA], and streptococcal collagen-like protein B [SclB]) were found to interact with beta 2-GPI. Only binding to protein H induces a conformational change in beta 2-GPI, thereby exposing a cryptic epitope for APS-related autoantibodies. 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 beta 2-GPI. Patients with pharyngotonsillitis caused by S. pyogenes who developed anti-protein H antibodies also generated anti- beta 2-GPI antibodies. Conclusions:Our study has demonstrated that a bacterial protein can induce a conformational change in beta 2-GPI, resulting in the formation of anti beta 2-GPI autoantibodies. This constitutes a novel mechanism for the formation of anti- beta 2-GPI autoantibodies.
ISSN:1538-7933
1538-7836
DOI:10.1111/j.1538-7836.2011.04532.x