Anti-β2 glycoprotein-I domain 1 antiphospholipid antibodies as a marker for adverse pregnancy outcomes

Lupus anticoagulant (LA) is the strongest predictor of 2nd and 3rd trimester adverse pregnancy outcome (APO) in systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). Antibodies against β2 glycoprotein-I (β2GPI) are also important in APS, particularly those against domain 1 (aD1), but data regarding their predictive value for APOs are limited. We investigate the value of aD1 for predicting APO in a high-risk population. Data were obtained from a prospective cohort of pregnant patients with antiphospholipid antibodies (aPL) meeting international criteria, with SLE (N=59) or without SLE (N=106), or SLE only (N=100) (PROMISSE study; NCT00198068). aD1 levels from early pregnancy sera were quantified using the QUANTA Flash® system; thresholds for positivity were determined using sera from 125 healthy, non-pregnant female controls. APO was defined as delivery at < 34 wks GA for preeclampsia or placental insufficiency or fetal death >10 wks GA. ROC analysis and Youden’s index were used to determine the optimal cut point for predicting APO. Logistic regression was performed to evaluate independent associations of individual antibody tests and baseline characteristics with APO risk. aD1 cut point associated with APO among aPL patients (6.6 CU, per Youden Index, Figure 1A) was 95th percentile among controls. Using this cutoff, sensitivity, specificity, positive predictive value and negative predictive value are 91%, 46%, 26% and 96%, respectively (Figure 1B). aD1 (aOR=6.3, p=0.002) and LA (aOR=5.8, p< 0.001) positivity were both significantly associated with APO after controlling for other laboratory and baseline characteristics (Table 1A). APO significantly differed by aD1 and LA (p< 0.001, Table 1B). In subjects with aPL meeting international criteria, with SLE or without SLE, or SLE only, aD1 is a significant independent predictor of APO. aD1 and LA are both independently associated with APO. aD1 may contribute additional information beyond that of LA alone in a high-risk population.View Large Image Figure ViewerDownload Hi-res image Download (PPT)