title: Autoantibodies to domain 1 of beta 2 glycoprotein I determined using a novel chemiluminescence immunoassay demonstrate association with thrombosis in patients with antiphospholipid syndrome.
abstract: BACKGROUND
  Antibodies to the domain 1 of beta 2 glycoprotein I (β2GPI-D1) have been suggested as a risk marker for thrombosis in patients with the antiphospholipid syndrome (APS). This cross-sectional study aimed to analyze the clinical utility of a novel chemiluminescence assay for the detection of anti-β2GPI-D1 antibodies.
  
  
  METHODS
  Sera collected from patients with primary or secondary APS (n = 106; 72 with and 34 without history of thrombosis) and controls (n = 272) were tested for anti-β2GPI-D1 IgG by chemiluminescence assay (QUANTA Flash) and by two anti-β2GPI IgG assays (QUANTA Lite and QUANTA Flash β2GPI IgG).
  
  
  RESULTS
  Anti-β2GPI-D1 IgG titers were significantly higher in patients with thrombosis (P = 0.0032) than those without. At the cut-off of 20 units, which yielded a 99.5% specificity, 24 of 72 (34.9%) patients with thrombosis and four of 34 (11.8%) without thrombosis were anti-β2GPI-D1 IgG positive (odds ratio, OR = 4.0). By further optimizing the cut-off specifically for correlation with thrombosis, 20.8% of the patients with thrombosis and 2.9% of the patients without thrombosis were positive (OR = 8.7). The ORs were significantly lower for antibodies to the full-length β2GPI by either the chemiluminescence assay or ELISA. Using the anti-β2GPI chemiluminescence assay, the OR was 2.3 (recommended cut-off of 20 CU) or 4.1 (optimal cut-off 164.6 CU). Using the anti-β2GPI ELISA, the OR was 2.7 (recommended cut-off of 20 units) or 3.7 (optimal cut-off 7.6 units).
  
  
  CONCLUSIONS
  These data indicate that anti-β2GPI-D1 IgG are present more frequently and in higher titers in APS patients with thrombotic complications than in those without.The novel β2GPI-D1 chemiluminescence assay appears to be superior to full-length β2GPI assays for the risk assessment of thrombotic events in APS patients.
authors.affiliation: Inova Diagnostics, Inc., San Diego, USA mmahler@inovadx.com m.mahler.job@web.de.
authors.forename: M
authors.initials: M
authors.lastname: Mahler
authors.affiliation: Inova Diagnostics, Inc., San Diego, USA.
authors.forename: R
authors.initials: R
authors.lastname: Albesa
authors.affiliation: Inova Diagnostics, Inc., San Diego, USA.
authors.forename: N
authors.initials: N
authors.lastname: Zohoury
authors.affiliation: Academic Department of Vascular Surgery, King's College London, London, UK.
authors.forename: M L
authors.initials: ML
authors.lastname: Bertolaccini
authors.affiliation: Graham Hughes Lupus Research Laboratory, King's College London School of Medicine, London, UK.
authors.forename: O
authors.initials: O
authors.lastname: Ateka-Barrutia
authors.affiliation: Graham Hughes Lupus Research Laboratory, King's College London School of Medicine, London, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Rodriguez-Garcia
authors.affiliation: Inova Diagnostics, Inc., San Diego, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Norman
authors.affiliation: Graham Hughes Lupus Research Laboratory, King's College London School of Medicine, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Khamashta
mesh_terms: D017153:Antibodies, Anticardiolipin / Q000097:blood*; D016736:Antiphospholipid Syndrome / Q000150:complications*; D003430:Cross-Sectional Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008163:Luminescent Measurements / Q000379:methods*; D012307:Risk Factors; D013927:Thrombosis / Q000150:complications*; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D017153:Antibodies, Anticardiolipin; D007074:Immunoglobulin G; D053482:beta 2-Glycoprotein I
keywords: Autoantibodies; Domain 1; antiphospholipid syndrome; beta 2 glycoprotein I; thrombosis