Unveiling the clinical spectrum: Exploring the role of anti-β2glycoprotein-1 antibodies (anti-β2GPI) in antiphospholipid syndrome suspects

Objectives: The objectives of this study were to determine the prevalence of anti-beta 2glycoprotein-1 antibodies (anti-beta 2GPI) in Pakistani patients clinically suspected to have antiphospholipid syndrome (APS) and assess their association with clinical manifestations. Introduction: The antiphospholipid syndrome (APS) is a complex disorder characterized by recurrent thrombotic and obstetric complications. Methods: An analytical cross-sectional study was conducted at Aga Khan University Hospital from January to June 2022, after obtaining ethical approval (ERC ID: 2021-6404-19580). A total of 133 patients aged 18-60 years, clinically suspected of having APS based on the updated international consensus (Sydney) classification criteria, were recruited. Anti-beta 2GPI antibodies were tested using the same blood samples provided for aCL testing, with verbal consent. Demographic, clinical, and biochemical data were collected via a structured questionnaire, while information on lupus anticoagulant testing was retrospectively obtained from prior records. Results: The study included 120 females (90.2%) and 13 males (9.8%) with a mean age of 31.3 +/- 8.8 years. Predominant clinical manifestations included unexplained miscarriages at >10 weeks of gestation (n = 77/120 female, 64.2%), while deep venous thrombosis (DVT) was a common non-obstetric clinical feature (n = 18/133, 13.5%). The median level of anti-beta 2GPI was 2.12 U/ml (1.34-7.04) and 7.5% (n = 10) were positive. Of the 10 positive patients, 2 displayed positive anti-beta 2GPI while concurrently testing negative for other aPL antibodies. A significant association was identified between the presence of anti-beta 2GPI and the occurrence of DVT and other venous thromboembolic events (VTE). Conclusion: This study highlights the prevalence and diagnostic utility of anti-beta 2GPI in Pakistani patients suspected of APS, identifying cases missed by other aPL tests and showing significant associations with thrombotic manifestations like DVT and VTE. However, the cross-sectional design, lack of confirmatory testing, and absence of locally derived cut-offs limit causal inferences.