Premium
Role of anti‐domain 1‐β 2 glycoprotein I antibodies in the diagnosis and risk stratification of antiphospholipid syndrome
Author(s) -
De Craemer A.S.,
Musial J.,
Devreese K. M. J.
Publication year - 2016
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13389
Subject(s) - antiphospholipid syndrome , medicine , lupus anticoagulant , antibody , immunology , autoantibody , immunoassay , odds ratio , immunoglobulin g , gastroenterology
Essentials Antibodies to domain 1 of β 2 glycoprotein I (aD1) are a subset of antiphospholipid antibodies. We evaluated the added diagnostic value of an automated aD1 assay in antiphospholipid syndrome. AD1 IgG correctly classifies patients at risk for thrombosis. Agreement between aD1 and aβ2GPI IgG is high, limiting the added value of aD1 in our setting.Click to hear Professor de Groot's perspective on new mechanistic understanding in antiphospholipid syndromeSummary Background Laboratory diagnosis of antiphospholipid syndrome ( APS ) includes lupus anticoagulant ( LAC ), anticardiolipin ( aCL ) or anti‐β 2 glycoprotein I (aβ 2 GPI ) antibodies. Antibodies targeting domain 1 of β 2 GPI ( aD 1) constitute a pathogenic subset of autoantibodies. Objectives In this cohort study, we determined the clinical performance characteristics, additional diagnostic value and the contribution to APS risk stratification of an automated aD 1 assay. Patients/Methods LAC , aCL , aβ 2 GPI and aD 1 IgG were measured in 101 APS patients, 123 patients with autoimmune disorders, 82 diseased controls and 120 healthy controls. aD 1 antibodies were detected by QUANTA Flash ® Beta2 GPI ‐Domain 1 chemiluminescence immunoassay. Results With a cut‐off value of 20.0 CU , the aD 1 IgG assay identifies APS patients in a clinically affected patient cohort with a sensitivity of 53.5% and specificity of 98.8%. It implied a high odds ratio ( OR ) for clinical events ( OR , 17.0; 95% confidence interval [ CI ], 7.1–40.5). aD 1 IgG did not add diagnostic value to the formal aPL panel because aβ 2 GPI IgG was nearly as specific but more sensitive for APS (sensitivity 56.4%) with a higher OR for clinical events (36.2; 95% CI , 11.1–117.9). High aD 1 titers identify triple‐positive patients and patients with thrombosis in a β 2 GPI ‐dependent LAC ‐positive population. Agreement between aD 1 IgG and aβ 2 GPI IgG was high (positive and negative agreement 91.7% and 98.4%, respectively). Conclusion Detection of aD 1 IgG correctly classifies patients at risk of thrombosis. However, the contribution of aD 1 IgG to APS diagnosis and risk stratification depends upon the solid phase assays used for aCL and aβ 2 GPI detection.