857: Proteomic biomarkers in mid-trimester amniotic fluid for adverse outcomes in pregnant women with SLE

Abstract

Pregnant women with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcomes (APOs) due to abnormal placentation. Identifying patients destined for APO early in pregnancy would significantly improve their obstetric outcomes. We sought to identify potential proteomic biomarkers in mid-trimester amniotic fluid of pregnant women with SLE for the prediction of APOs. The study population included 35 pregnant women with SLE who underwent clinically indicated amniocentesis at 15-24 weeks of gestation. Patients were divided into two groups: 19 women with normal pregnancy outcome (Group 1=control group) and 16 women who developed APOs (Group 2=APO group). APO was defined as the development of at least one of the followings: preeclampsia, fetal death in utero, neonatal death before hospital discharge, indicated preterm birth <36 weeks, and small for gestational age (<5th percentile) at birth. Stored samples of amniotic fluids were analyzed using mass spectrometry-based proteomics. In a discovery phase, we analyzed 9 patients (4 in Group 1 and 5 in Group 2) with data-dependent acquisition (DDA) approach. In a verification phase, we analyzed the remained 26 patients (15 in Group 1 and 11 in Group 2) using data- independent acquisition (DIA) method. Hierarchical clustering was performed based on the Euclidean distance and the average linkage. In the discovery phase, 44 proteins were differentially expressed between Group 1 and Group 2. In a verification phase, differentially expressed proteins (DEPs) were verified in independent samples using DIA method. Four proteins including FLNA (filamin A), SVEP1 (sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1), LCAT (lecithin-cholesterol acyltransferase), and TGM2 (transglutaminase 2) were differentially expressed both in discovery and verification phase. In order to select the best combination of proteins for predicting adverse outcomes, three-fold cross validation (CV) with repetition of 100 times was performed. The multi-marker model with 3 biomarkers (SVEP1, LCAT, TGM2) had a high discriminatory power to distinguish between the two groups (the area under the receiver operating characteristic, AUROC = 0.855, p<0.001). Our result indicates that increased expression of SVEP1, LCAT, and TGM2 in mid-trimester amniotic fluid may predict APOs in women with SLE. A large scale prospective study is warranted to verify this finding.