M Mahler1, R Albesa2, N Zohoury2, M L Bertolaccini3, O Ateka-Barrutia4, J L Rodriguez-Garcia4, G L Norman2, M Khamashta4. 1. Inova Diagnostics, Inc., San Diego, USA mmahler@inovadx.com m.mahler.job@web.de. 2. Inova Diagnostics, Inc., San Diego, USA. 3. Academic Department of Vascular Surgery, King's College London, London, UK. 4. Graham Hughes Lupus Research Laboratory, King's College London School of Medicine, London, UK.
Abstract
INTRODUCTION: 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. PATIENTS AND 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). CONCLUSION: 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.
INTRODUCTION: 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. PATIENTS AND 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). CONCLUSION: These data indicate that anti-β2GPI-D1 IgG are present more frequently and in higher titers in APSpatients 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 APSpatients.
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