Induction of anti-β2 -glycoprotein I autoantibodies in mice by protein H of Streptococcus pyogenes

G. M. A. van O S, J. C. M. Meijers, Ç Agar, M. Valls Seron, J. A. Marquart, P. Åkesson, R. T. Urbanus, R. H. W. M. Derksen, H. Herwald, M. Mörgelin, P. G. D E Groot

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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. To evaluate the potential of S. pyogenes-derived proteins to induce anti-β(2) -GPI autoantibodies. 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. 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
Original languageEnglish
Pages (from-to)2447-2456
JournalJournal of thrombosis and haemostasis
Issue number12
Publication statusPublished - 2011

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