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

BackgroundAnti-& beta;2GPI-domain I (& beta;2GPI-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-& beta;2GPI-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-& beta;2GPI-DI IgG, accounting for 77.5% of those with anti-& beta;2GPI IgG positivity. It is shown that 96.4% of those with anti-& beta;2GPI-DI IgG also showed triple positivity in classic antiphospholipid antibodies (aPLs). The positivity of anti-& beta;2GPI-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-& beta;2GPI-DI IgG, especially for thrombocytopenia and APS nephropathy. In multivariable analysis, anti-& beta;2GPI-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-& beta;2GPI-DI IgG also showed a tendency of more extra-criteria events, but not thrombotic events. Anti-& beta;2GPI-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-& beta;2GPI-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.