Anti-β2GPI domain 1 antibodies stratify high risk of thrombosis and late pregnancy morbidity in a large cohort of Chinese patients with antiphospholipid syndrome

Abstract

IntroductionAnti-β2GPI-Domain 1 (β2GPI-D1) antibodies are considered to be a pathogenic subset of anti-β2GPI antibodies and have been strongly associated with thrombosis and pregnancy morbidity in patients with antiphospholipid syndrome (APS). We evaluated the clinical utility of anti-β2GPI-D1 IgG antibodies for stratifying the risk of thrombosis and/or pregnancy morbidity (PM) in a cohort of Chinese patients with APS and also assessed its correlation with the Global Anti-Phospholipid Syndrome Score (GAPSS). Materials and methodsSera and plasma from 192 consecutive APS patients, 17 aPL carriers, 193 patients with other systemic autoimmune diseases, and 120 healthy controls were collected and the presence of aCL IgG/IgM, anti-β2GPI IgG/IgM and anti-β2GPI-D1 IgG antibodies were assessed by chemiluminescence assays (CIA). Detection of LAC was performed according to international guidelines with the use of screening, mixing and confirmation tests. Anti-phosphatidylserine-prothrombin (aPS/PT) IgG and IgM antibodies were detected by commercial ELISA kits. ResultsAnti-β2GPI-D1 IgG antibodies showed high specificity (97.12%) and moderate sensitivity (64.32%) for the diagnosis of APS. Anti-β2GPI-D1 antibodies levels were significantly higher in patients with triple aPL positivity than in those with double (P < 0.001) and single positive aPL (P < 0.001) and correlated well with the GAPSS (rho = 0.60, P < 0.001). Anti-β2GPI-D1 antibodies presented with a higher prevalence and higher titers in patients with late pregnancy morbidity (≥10 weeks) and thrombotic APS compared to those with early pregnancy (<10 weeks) morbidity. Higher anti-β2GP1-D1 antibodies titers effectively distinguished APS from other autoimmune diseases. ConclusionThis study suggests a predictive role of anti-β2GPI-D1 IgG antibodies as a strong risk factor for both thrombotic and obstetric APS (OAPS), especially for stratification comparing early PM with late PM and thrombosis.