RESUMEN
BACKGROUND: The antiphospholipid syndrome (APS) is characterized by the persistent presence of anti-ß(2) -glycoprotein I (ß(2) -GPI) autoantibodies. ß(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. ß(2) -GPI has been shown to interact with Streptococcus pyogenes. OBJECTIVE: To evaluate the potential of S. pyogenes-derived proteins to induce anti-ß(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 ß(2) -GPI. Only binding to protein H induces a conformational change in ß(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 ß(2) -GPI. Patients with pharyngotonsillitis caused by S. pyogenes who developed anti-protein H antibodies also generated anti-ß(2) -GPI antibodies. CONCLUSIONS: Our study has demonstrated that a bacterial protein can induce a conformational change in ß(2) -GPI, resulting in the formation of antiß(2) -GPI autoantibodies. This constitutes a novel mechanism for the formation of anti-ß(2) -GPI autoantibodies.