Metabolic Biomarkers In Midtrimester Maternal Plasma Can Accurately Predict Adverse Pregnancy Outcome in Patients with SLE

Seung Mi Lee, Eun Mi Lee, Jin Kyun Park, Hae Sun Jeon, Sohee Oh, Subeen Hong, Young Mi Jung, Byoung Jae Kim, Sun Min Kim, Errol R. Norwitz, Eun Bong Lee, Souphaphone Louangsenlath, Chan Wook Park, Jong Kwan Jun, Joong Shin Park, Do Yup Lee

Research output: Contribution to journalArticle

Abstract

Patients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcome (APO). Accurate prediction of APO is critical to identify, counsel, and manage these high-risk patients. We undertook this study to identify novel biomarkers in mid-trimester maternal plasma to identify pregnant patients with SLE at increased risk of APOs. The study population consisted of pregnant women whose plasma was taken in mid-trimester and available for metabolic signature: (1) SLE and normal pregnancy outcome (Group 1, n = 21); (2) SLE with APO (Group 2, n = 12); and (3) healthy pregnant controls (Group 3, n = 10). Mid-trimester maternal plasma was analyzed for integrative profiles of primary metabolite and phospholipid using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and liquid chromatography Orbitrap mass spectrometry (LC-Orbitrap MS). For performance comparison and validation, plasma samples were analyzed for sFlt-1/PlGF ratio. In the study population, APO developed in 12 of 33 women with SLE (36%). Metabolite profiling of mid-trimester maternal plasma samples identified a total of 327 metabolites using GC-TOF MS and LC-Orbitrap MS. Partial least squares discriminant analysis (PLS-DA) showed clear discrimination among the profiles of SLE groups and healthy pregnant controls (Groups 1/2 vs. 3). Moreover, direct comparison between Groups 1 and 2 demonstrated that 4 primary metabolites and 13 lipid molecules were significantly different. Binary logistic regression analysis suggested a potential metabolic biomarker model that could discriminate Groups 1 and 2. Receiver operating characteristic (ROC) analysis revealed the best predictability for APO with the combination model of two metabolites (LysoPC C22:5 and tryptophan) with AUC of 0.944, comparable to the AUC of sFlt-1/PlGF (AUC 0.857). In conclusion, metabolic biomarkers in mid-trimester maternal plasma can accurately predict APO in patients with SLE.

Original languageEnglish
Article number15169
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019

Fingerprint

Second Pregnancy Trimester
Pregnancy Outcome
Systemic Lupus Erythematosus
Biomarkers
Mothers
Mass Spectrometry
Area Under Curve
Liquid Chromatography
Gas Chromatography
Control Groups
Discriminant Analysis
Least-Squares Analysis
ROC Curve
Tryptophan
Population
Pregnant Women
Phospholipids
Logistic Models
Regression Analysis
Lipids

Cite this

Lee, Seung Mi ; Lee, Eun Mi ; Park, Jin Kyun ; Jeon, Hae Sun ; Oh, Sohee ; Hong, Subeen ; Jung, Young Mi ; Kim, Byoung Jae ; Kim, Sun Min ; Norwitz, Errol R. ; Lee, Eun Bong ; Louangsenlath, Souphaphone ; Park, Chan Wook ; Jun, Jong Kwan ; Park, Joong Shin ; Lee, Do Yup. / Metabolic Biomarkers In Midtrimester Maternal Plasma Can Accurately Predict Adverse Pregnancy Outcome in Patients with SLE. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
@article{f5effb76b4f248f5a12566ef377aff84,
title = "Metabolic Biomarkers In Midtrimester Maternal Plasma Can Accurately Predict Adverse Pregnancy Outcome in Patients with SLE",
abstract = "Patients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcome (APO). Accurate prediction of APO is critical to identify, counsel, and manage these high-risk patients. We undertook this study to identify novel biomarkers in mid-trimester maternal plasma to identify pregnant patients with SLE at increased risk of APOs. The study population consisted of pregnant women whose plasma was taken in mid-trimester and available for metabolic signature: (1) SLE and normal pregnancy outcome (Group 1, n = 21); (2) SLE with APO (Group 2, n = 12); and (3) healthy pregnant controls (Group 3, n = 10). Mid-trimester maternal plasma was analyzed for integrative profiles of primary metabolite and phospholipid using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and liquid chromatography Orbitrap mass spectrometry (LC-Orbitrap MS). For performance comparison and validation, plasma samples were analyzed for sFlt-1/PlGF ratio. In the study population, APO developed in 12 of 33 women with SLE (36{\%}). Metabolite profiling of mid-trimester maternal plasma samples identified a total of 327 metabolites using GC-TOF MS and LC-Orbitrap MS. Partial least squares discriminant analysis (PLS-DA) showed clear discrimination among the profiles of SLE groups and healthy pregnant controls (Groups 1/2 vs. 3). Moreover, direct comparison between Groups 1 and 2 demonstrated that 4 primary metabolites and 13 lipid molecules were significantly different. Binary logistic regression analysis suggested a potential metabolic biomarker model that could discriminate Groups 1 and 2. Receiver operating characteristic (ROC) analysis revealed the best predictability for APO with the combination model of two metabolites (LysoPC C22:5 and tryptophan) with AUC of 0.944, comparable to the AUC of sFlt-1/PlGF (AUC 0.857). In conclusion, metabolic biomarkers in mid-trimester maternal plasma can accurately predict APO in patients with SLE.",
author = "Lee, {Seung Mi} and Lee, {Eun Mi} and Park, {Jin Kyun} and Jeon, {Hae Sun} and Sohee Oh and Subeen Hong and Jung, {Young Mi} and Kim, {Byoung Jae} and Kim, {Sun Min} and Norwitz, {Errol R.} and Lee, {Eun Bong} and Souphaphone Louangsenlath and Park, {Chan Wook} and Jun, {Jong Kwan} and Park, {Joong Shin} and Lee, {Do Yup}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-019-51285-8",
language = "English",
volume = "9",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

Lee, SM, Lee, EM, Park, JK, Jeon, HS, Oh, S, Hong, S, Jung, YM, Kim, BJ, Kim, SM, Norwitz, ER, Lee, EB, Louangsenlath, S, Park, CW, Jun, JK, Park, JS & Lee, DY 2019, 'Metabolic Biomarkers In Midtrimester Maternal Plasma Can Accurately Predict Adverse Pregnancy Outcome in Patients with SLE', Scientific Reports, vol. 9, no. 1, 15169. https://doi.org/10.1038/s41598-019-51285-8

Metabolic Biomarkers In Midtrimester Maternal Plasma Can Accurately Predict Adverse Pregnancy Outcome in Patients with SLE. / Lee, Seung Mi; Lee, Eun Mi; Park, Jin Kyun; Jeon, Hae Sun; Oh, Sohee; Hong, Subeen; Jung, Young Mi; Kim, Byoung Jae; Kim, Sun Min; Norwitz, Errol R.; Lee, Eun Bong; Louangsenlath, Souphaphone; Park, Chan Wook; Jun, Jong Kwan; Park, Joong Shin; Lee, Do Yup.

In: Scientific Reports, Vol. 9, No. 1, 15169, 01.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Metabolic Biomarkers In Midtrimester Maternal Plasma Can Accurately Predict Adverse Pregnancy Outcome in Patients with SLE

AU - Lee, Seung Mi

AU - Lee, Eun Mi

AU - Park, Jin Kyun

AU - Jeon, Hae Sun

AU - Oh, Sohee

AU - Hong, Subeen

AU - Jung, Young Mi

AU - Kim, Byoung Jae

AU - Kim, Sun Min

AU - Norwitz, Errol R.

AU - Lee, Eun Bong

AU - Louangsenlath, Souphaphone

AU - Park, Chan Wook

AU - Jun, Jong Kwan

AU - Park, Joong Shin

AU - Lee, Do Yup

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Patients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcome (APO). Accurate prediction of APO is critical to identify, counsel, and manage these high-risk patients. We undertook this study to identify novel biomarkers in mid-trimester maternal plasma to identify pregnant patients with SLE at increased risk of APOs. The study population consisted of pregnant women whose plasma was taken in mid-trimester and available for metabolic signature: (1) SLE and normal pregnancy outcome (Group 1, n = 21); (2) SLE with APO (Group 2, n = 12); and (3) healthy pregnant controls (Group 3, n = 10). Mid-trimester maternal plasma was analyzed for integrative profiles of primary metabolite and phospholipid using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and liquid chromatography Orbitrap mass spectrometry (LC-Orbitrap MS). For performance comparison and validation, plasma samples were analyzed for sFlt-1/PlGF ratio. In the study population, APO developed in 12 of 33 women with SLE (36%). Metabolite profiling of mid-trimester maternal plasma samples identified a total of 327 metabolites using GC-TOF MS and LC-Orbitrap MS. Partial least squares discriminant analysis (PLS-DA) showed clear discrimination among the profiles of SLE groups and healthy pregnant controls (Groups 1/2 vs. 3). Moreover, direct comparison between Groups 1 and 2 demonstrated that 4 primary metabolites and 13 lipid molecules were significantly different. Binary logistic regression analysis suggested a potential metabolic biomarker model that could discriminate Groups 1 and 2. Receiver operating characteristic (ROC) analysis revealed the best predictability for APO with the combination model of two metabolites (LysoPC C22:5 and tryptophan) with AUC of 0.944, comparable to the AUC of sFlt-1/PlGF (AUC 0.857). In conclusion, metabolic biomarkers in mid-trimester maternal plasma can accurately predict APO in patients with SLE.

AB - Patients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcome (APO). Accurate prediction of APO is critical to identify, counsel, and manage these high-risk patients. We undertook this study to identify novel biomarkers in mid-trimester maternal plasma to identify pregnant patients with SLE at increased risk of APOs. The study population consisted of pregnant women whose plasma was taken in mid-trimester and available for metabolic signature: (1) SLE and normal pregnancy outcome (Group 1, n = 21); (2) SLE with APO (Group 2, n = 12); and (3) healthy pregnant controls (Group 3, n = 10). Mid-trimester maternal plasma was analyzed for integrative profiles of primary metabolite and phospholipid using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and liquid chromatography Orbitrap mass spectrometry (LC-Orbitrap MS). For performance comparison and validation, plasma samples were analyzed for sFlt-1/PlGF ratio. In the study population, APO developed in 12 of 33 women with SLE (36%). Metabolite profiling of mid-trimester maternal plasma samples identified a total of 327 metabolites using GC-TOF MS and LC-Orbitrap MS. Partial least squares discriminant analysis (PLS-DA) showed clear discrimination among the profiles of SLE groups and healthy pregnant controls (Groups 1/2 vs. 3). Moreover, direct comparison between Groups 1 and 2 demonstrated that 4 primary metabolites and 13 lipid molecules were significantly different. Binary logistic regression analysis suggested a potential metabolic biomarker model that could discriminate Groups 1 and 2. Receiver operating characteristic (ROC) analysis revealed the best predictability for APO with the combination model of two metabolites (LysoPC C22:5 and tryptophan) with AUC of 0.944, comparable to the AUC of sFlt-1/PlGF (AUC 0.857). In conclusion, metabolic biomarkers in mid-trimester maternal plasma can accurately predict APO in patients with SLE.

UR - http://www.scopus.com/inward/record.url?scp=85074093181&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-51285-8

DO - 10.1038/s41598-019-51285-8

M3 - Article

C2 - 31645572

AN - SCOPUS:85074093181

VL - 9

JO - Scientific reports

JF - Scientific reports

SN - 2045-2322

IS - 1

M1 - 15169

ER -