title: Induction of anti-β2 -glycoprotein I autoantibodies in mice by protein H of Streptococcus pyogenes.
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.
  
  
  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.
authors: Department of Clinical Chemistry and Hematology, University Medical Center, CX, Utrecht, the Netherlands.
authors: G M A
authors: GM
authors: van Os
authors: J C M
authors: JC
authors: Meijers
authors: Ç
authors: Ç
authors: Agar
authors: M V
authors: MV
authors: Seron
authors: J A
authors: JA
authors: Marquart
authors: P
authors: P
authors: Åkesson
authors: R T
authors: RT
authors: Urbanus
authors: R H W M
authors: RH
authors: Derksen
authors: H
authors: H
authors: Herwald
authors: M
authors: M
authors: Mörgelin
authors: P G
authors: PG
authors: D E Groot
mesh_terms: D000818:Animals; D016736:Antiphospholipid Syndrome / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D013297:Streptococcus pyogenes / Q000502:physiology*; D020349:Surface Plasmon Resonance; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001426:Bacterial Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D053482:beta 2-Glycoprotein I; C064006:protein H, Streptococcus