Induction of Auto-Antibodies Against β(2) -Glycoprotein I in Mice by Protein H of Streptococcus Pyogenes.

Research output: Contribution to journalArticle

Abstract

Background: The antiphospholipid syndrome (APS) is characterized by the persistent presence of auto-antibodies against β(2) -Glycoprotein I (β(2) -GPI). β(2) -GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish-hook shape 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: Here we evaluated the potential of S. pyogenes derived proteins to induce auto-antibodies against β(2) -GPI. Methods and results: Four S. pyogenes surface proteins (M1 protein, protein H, SclA and 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 auto-antibodies. 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 antibodies towards protein H also generated anti-β(2) -GPI antibodies. Conclusion: Our study demonstrated that a bacterial protein can induce a conformational change in β(2) -GPI resulting in the formation of auto-antibodies against β(2) -GPI. This constitutes a novel mechanism for the formation of auto-antibodies against β(2) -GPI.

Details

Authors
  • G M A van Os
  • J C M Meijers
  • C Ağar
  • M Valls Serón
  • J A Marquart
  • Per Åkesson
  • R T Urbanus
  • R H W M Derksen
  • Heiko Herwald
  • Matthias Mörgelin
  • P G de Groot
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems

Keywords

  • antiphospholipid syndrome, autoantibodies, ss 2-glycoprotein I
Original languageEnglish
Pages (from-to)2447-2456
JournalJournal of Thrombosis and Haemostasis
Volume9
Issue number12
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes