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

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Abstract

Background:The antiphospholipid syndrome (APS) is characterized by the persistent presence of anti-β 2-glycoprotein I (β 2-GPI) autoantibodies. β 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. β 2-GPI has been shown to interact with Streptococcus pyogenes. Objective:To evaluate the potential of S. pyogenes-derived proteins to induce anti-β 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 β 2-GPI. Only binding to protein H induces a conformational change in β 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 β 2-GPI. Patients with pharyngotonsillitis caused by S. pyogenes who developed anti-protein H antibodies also generated anti-β 2-GPI antibodies. Conclusions:Our study has demonstrated that a bacterial protein can induce a conformational change in β 2-GPI, resulting in the formation of antiβ 2-GPI autoantibodies. This constitutes a novel mechanism for the formation of anti-β 2-GPI autoantibodies. © 2011 International Society on Thrombosis and Haemostasis.

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Van Os, G. M. A., Meijers, J. C. M., Agar, Ç., Seron, M. V., Marquart, J. A., Åkesson, P., … De Groot, P. G. (2011). Induction of anti-β 2-glycoprotein I autoantibodies in mice by protein H of Streptococcus pyogenes. Journal of Thrombosis and Haemostasis, 9(12), 2447–2456. https://doi.org/10.1111/j.1538-7836.2011.04532.x

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