Proteomic biomarkers in mid-trimester amniotic fluid associated with adverse pregnancy outcomes in patients with systemic lupus erythematosus.

Hae Sun Jeon,Seung Mi Lee,Chan-Wook Park,Sohee Oh,Eun Bong Lee,Young Mi Jung,Joong Shin Park,Jin Kyun Park,Dohyun Han,Jong Kwan Jun,Frank T Spradley

doi:10.1371/journal.pone.0235838

Hae Sun Jeon, Seung Mi Lee + Show 9 more

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https://doi.org/10.1371/journal.pone.0235838

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Abstract

We aimed to explore the proteomic profiles of mid-trimester amniotic fluid in pregnant women with systemic lupus erythematosus (SLE) according to the occurrence of adverse pregnancy outcome (APO). 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 according to pregnancy outcomes: SLE patients without APO (Group 1) and SLE patients with APO (Group 2). Stored samples of amniotic fluid were analyzed using mass spectrometry (MS)-based proteomics with two-step approach, consisting of discovery and verification phase. In the discovery phase, 44 proteins were differentially expressed between Group 1 and Group 2. In the verification phase, differentially expressed proteins (DEPs) were verified in independent samples using DIA method. Four proteins including filamin A (FLNA), sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1), lecithin-cholesterol acyltransferase (LCAT), and transglutaminase 2 (TGM2) were differentially expressed both in discovery and verification phase. To select the best combination of proteins for discriminating two groups, three-fold cross validation (CV) with repetition of one hundred times was performed. The multi-marker model with three biomarkers (SVEP1, LCAT, TGM2) had a high discriminatory power to distinguish between the two groups (the area under the receiver operating characteristic, AUROC = 0.946, p <0.001). Our results indicate that the expression of FLNA, SVEP1, LCAT, and TGM2 in mid-trimester amniotic fluid was increased in SLE patients with APO (Group 2). A large-scale prospective study is warranted to verify this finding.

Highlights

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a broad spectrum of symptoms and clinical courses characterized by remissions and flares [1]
According to the occurrence of adverse pregnancy outcome (APO), the study population was classified into two groups: 1) SLE patients without APO (Group 1, n = 19); 2) SLE patients with APO (Group 2, n = 16)
In SLE patients with APO (Group 2), preeclampsia developed in 62.5% of cases, indicated preterm delivery in 68.8%, small for gestational age at birth in 60%, fetal death in utero in 25%, and neonatal death in none of the cases

Summary

Introduction

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a broad spectrum of symptoms and clinical courses characterized by remissions and flares [1]. It predominantly affects women in their reproductive years, with a female to male incidence ratio of 9:1, peaking at the age of 30–39 years [2, 3]. According to the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study, the first multicenter, prospective observational study of pregnancies in women with SLE, APOs occurred in 19.0% of pregnancies; fetal death in 4%, neonatal death in 1%, preterm delivery in 9%, and small-for-gestational-age neonate in 10% [9]. Despite the significant impact of SLE on pregnancy outcomes, the mechanisms by which pregnancy complications occur in SLE patients have been complex and incompletely understood

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