Autoantibodies to domain 1 of beta 2 glycoprotein I determined using a novel chemiluminescence immunoassay demonstrate association with thrombosis in patients with antiphospholipid syndrome.

INTRODUCTION: Antibodies to the domain 1 of beta 2 glycoprotein I (ß2GPI-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-ß2GPI-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-ß2GPI-D1 IgG by chemiluminescence assay (QUANTA Flash) and by two anti-ß2GPI IgG assays (QUANTA Lite and QUANTA Flash ß2GPI IgG). RESULTS: Anti-ß2GPI-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-ß2GPI-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 ß2GPI by either the chemiluminescence assay or ELISA. Using the anti-ß2GPI 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-ß2GPI 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-ß2GPI-D1 IgG are present more frequently and in higher titers in APS patients with thrombotic complications than in those without.The novel ß2GPI-D1 chemiluminescence assay appears to be superior to full-length ß2GPI assays for the risk assessment of thrombotic events in APS patients.

Role of antiphospholipid score and anti-ß2-glycoprotein I Domain I autoantibodies in the diagnosis of antiphospholipid syndrome.

BACKGROUND: Antiphospholipid syndrome (APS) is characterized by the presence circulating antiphospholipid (aPL) antibodies in patients with thrombosis or pregnancy morbidity. Recently it has been shown that multiple positive results define a higher risk of clinical manifestation in APS patients. However, utilizing combined results generates challenges for a physician. Therefore, the antiphospholipid score. (aPL-S), a new variable that encompasses all aPL assays, has been described. We analyze clinical performance of different aPL-Ss based on ELISA or chemiluminescent immunoassays (CIAs). METHODS: A total of 39 patients and 77 controls were included in this study. All patients were tested for lupus anticoagulant (LAC). In addition, IgM/IgG anticardiolipin (aCL) and anti-ß2 glycoprotein 1 (aß2GP1) autoantibodies were tested by ELISA and CIA. Anti-ß2GP1 Domain 1 IgG (D1) autoantibodies were tested by CIA. Three aPL-Ss were calculated (ELISA, CIA and CIA with D1 instead of ß2GP1 IgG) using the Otomo equation: aPL-S=5×exp([OR]-5)/4. RESULTS: IgG assays showed a good correlation while IgM assays showed moderate correlation. The relative risk of having clinical manifestation of APS was calculated for each aPL test. All three aPL-Ss were higher in individuals with thrombosis or pregnancy morbidity than in those without APS manifestations (p<0.001) and the prevalence of APS manifestations increased with increasing aPL-Ss. CONCLUSION: The CIAs are comparable with the ELISAs for the detection of aPL antibodies. aß2GPI-D1 antibodies seem to represent a strong indicator for clinical manifestations of APS. Any of the aPL-Ss studied represents a useful quantitative index for APS diagnosis and could be helpful to physicians in managing APS.