β2-Glycoprotein I Autoantibodies

Eiji Matsuura, Luis R. Lopez

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Elevated serum levels of antiphospholipid antibodies, venous or arterial thrombosis, and/or pregnancy morbidity (miscarriages, recurrent fetal loss) are the major serologic and clinical features of the antiphospholipid syndrome (APS). Antiphospholipid antibodies belong to a heterogeneous family of autoantibodies that play a crucial role in the development of thrombosis in patients with APS. These antibodies may react with negatively charged phospholipids, phospholipid/protein complexes, and certain plasma proteins attached to suitable surfaces (i.e., activated cell membranes, oxygenated polystyrene). Most antiphospholipid antibodies derived from patients with APS require the presence of certain plasma proteins for optimal phospholipid binding activity. β2-Glycoprotein I (β2GPI), a phospholipid-binding plasma protein, is now recognized as the most clinically relevant antigenic target for antiphospholipid antibodies. Antibodies to β2GPI are more specific for thrombosis (and APS) than anticardiolipin (aCL) antibodies. Recent prospective studies have shown that β2GPI-dependent aCL and anti-γ2GPI antibodies were significant predictors of arterial thrombosis (myocardial infarction and stroke). In addition to natural anticoagulant properties, β2GPI may also bind to oxidized low-density lipoprotein (oxLDL) likely to quench its proinflammatory and atherogenic effects. Circulating oxLDL/β2GPI complexes are immunogenic, and anti-oxLDL/β2GPI antibodies accelerate their macrophage uptake and the development of autoimmune-mediated atherothrombosis. Autoantibodies against oxLDL/β2GPI complexes strongly correlated with arterial thrombosis in patients with systemic lupus erythematosus (SLE) and APS. These findings suggest that β2GPI and anti-γ2GPI antibodies play a central pathogenic role in thrombosis, and particularly in autoimmune-mediated atherosclerosis.

Original languageEnglish
Title of host publicationAutoantibodies
Subtitle of host publicationThird Edition
PublisherElsevier B.V.
Pages689-698
Number of pages10
ISBN (Print)9780444563781
DOIs
Publication statusPublished - Dec 2013

Keywords

  • Anti-beta2GPI antibodies
  • Antiphospholipid antibodies
  • Antiphospholipid syndrome
  • Atherosclerosis
  • Beta2-glycoprotein I
  • Inflammation
  • Thrombosis

ASJC Scopus subject areas

  • Immunology and Microbiology(all)

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