title: Novel assays of thrombogenic pathogenicity in the antiphospholipid syndrome based on the detection of molecular oxidative modification of the major autoantigen β2-glycoprotein I.
abstract: OBJECTIVE
  Beta-2-glycoprotein I (β2 GPI) constitutes the major autoantigen in the antiphospholipid syndrome (APS), a common acquired cause of arterial and venous thrombosis. We recently described the novel observation that β2 GPI may exist in healthy individuals in a free thiol (biochemically reduced) form. The present study was undertaken to quantify the levels of total, reduced, and posttranslationally modified oxidized β2 GPI in APS patients compared to various control groups.
  
  
  METHODS
  In a retrospective multicenter analysis, the proportion of β2 GPI with free thiols in serum from healthy volunteers was quantified. Assays for measurement of reduced as well as total circulating β2 GPI were developed and tested in the following groups: APS (with thrombosis) (n=139), autoimmune disease with or without persistent antiphospholipid antibodies (aPL) but without APS (n=188), vascular thrombosis without APS or aPL (n=38), and healthy volunteers (n=91).
  
  
  RESULTS
  Total β2 GPI was significantly elevated in patients with APS (median 216.2 μg/ml [interquartile range 173.3-263.8]) as compared to healthy subjects (median 178.4 μg/ml [interquartile range 149.4-227.5] [P<0.0002]) or control patients with autoimmune disease or vascular thrombosis (both P<0.0001). The proportion of total β2 GPI in an oxidized form (i.e., lacking free thiols) was significantly greater in the APS group than in each of the 3 control groups (all P<0.0001).
  
  
  CONCLUSIONS
  This large retrospective multicenter study shows that posttranslational modification of β2 GPI via thiol-exchange reactions is a highly specific phenomenon in the setting of APS thrombosis. Quantification of posttranslational modifications of β2 GPI in conjunction with standard laboratory tests for APS may offer the potential to more accurately predict the risk of occurrence of a thrombotic event in the setting of APS.
authors: Department of Immunology, St. George Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors: Yiannis
authors: Y
authors: Ioannou
authors: Jing-Yun
authors: JY
authors: Zhang
authors: Miao
authors: M
authors: Qi
authors: Lu
authors: L
authors: Gao
authors: Jian Cheng
authors: JC
authors: Qi
authors: De-Min
authors: DM
authors: Yu
authors: Herman
authors: H
authors: Lau
authors: Allan D
authors: AD
authors: Sturgess
authors: Panayiotis G
authors: PG
authors: Vlachoyiannopoulos
authors: Haralampos M
authors: HM
authors: Moutsopoulos
authors: Anisur
authors: A
authors: Rahman
authors: Charis
authors: C
authors: Pericleous
authors: Tatsuya
authors: T
authors: Atsumi
authors: Takao
authors: T
authors: Koike
authors: Stephane
authors: S
authors: Heritier
authors: Bill
authors: B
authors: Giannakopoulos
authors: Steven A
authors: SA
authors: Krilis
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