Anti-β2GPI-domain I antibody is associated with extra-criteria manifestations in a large prospective antiphospholipid syndrome cohort in China

• Published in: Lupus science & medicine Vol. 10; no. 2; p. e000924
• Main Authors: Zhou, Yangzhong, Hu, Chaojun, Qi, Wanting, Long, Yin, Huang, Can, Wang, Qian, Tian, Xinping, Zhao, Jiuliang, Li, Mengtao, Zeng, Xiaofeng
• Format: Journal Article
• Language: English
• Published: London Lupus Foundation of America 01.08.2023; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Anemia; Antibodies; antiphospholipid antibodies; antiphospholipid syndrome; Autoimmune diseases; Biomarker Studies; Cardiovascular disease; Classification; Coronary vessels; Demographics; Hypertension; lupus erythematosus, systemic; Obstetrics; Thrombocytopenia; Thrombosis; Vein & artery diseases
• ISSN: 2053-8790; 2053-8790
• DOI: 10.1136/lupus-2023-000924

BackgroundAnti-β2GPI-domain I (β2GPI-DI) antibody is pathogenic in patients with antiphospholipid syndrome (APS), but its additional clinical associations and diagnostic value are controversial.MethodsA total of 378 patients were included, of which 119 patients diagnosed with primary APS, 50 with APS secondary to SLE (SAPS group), 209 with SLE without APS (SLE group). Serum anti-β2GPI-DI IgG was measured using chemiluminescent immunoassay. Extra-criteria manifestations were analysed, including thrombocytopenia, autoimmune haemolytic anaemia, valvular lesions, APS nephropathy and non-vascular neurological manifestations.ResultsIn 169 patients with APS, 55 (32.5%) were positive for anti-β2GPI-DI IgG, accounting for 77.5% of those with anti-β2GPI IgG positivity. It is shown that 96.4% of those with anti-β2GPI-DI IgG also showed triple positivity in classic antiphospholipid antibodies (aPLs). The positivity of anti-β2GPI-DI IgG was significantly associated with recurrent thrombosis before APS diagnosis (p=0.015), microvascular thrombosis (p=0.038), but not with pregnancy morbidity (PM). Notably, patients with extra-criteria manifestations showed significantly higher positivity (p=0.001) and titres (p<0.001) in anti-β2GPI-DI IgG, especially for thrombocytopenia and APS nephropathy. In multivariable analysis, anti-β2GPI-DI IgG positivity (OR 2.94, 95% CI 1.29 to 6.70), secondary APS, arterial hypertension and Coombs’ test positivity independently predicted extra-criteria manifestations (C-index 0.83, 95% CI 0.77 to 0.90). After a median follow-up of 25 months, patients with anti-β2GPI-DI IgG also showed a tendency of more extra-criteria events, but not thrombotic events. Anti-β2GPI-DI was positive among 8.1% of the SLE controls, and showed high specificity (91.9%) in diagnosing SAPS among patients with SLE as compared with classic aPLs.ConclusionAnti-β2GPI-DI IgG was associated with extra-criteria manifestations in patients with APS. Further studies are warranted to validate its predictive values and potential role in daily practice.