Feasibility of Multiplex Cytokine Profiling in Preterm Labor: Towards Biomarker Discovery

Preterm delivery affects approximately 10% of pregnancies worldwide and remains a major clinical challenge due to the lack of reliable early predictive tools. Existing strategies are often invasive, relying on blood or amniotic fluid samples and requiring complex processing. In this study, we descri...

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Main Authors: Ruth Llano, Inés Ardao, José Manuel Brea, Luz Romero, María P. Pata, Antón L. Martínez, Manuel Macía, María Isabel Loza
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/14/6/714
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author Ruth Llano
Inés Ardao
José Manuel Brea
Luz Romero
María P. Pata
Antón L. Martínez
Manuel Macía
María Isabel Loza
author_facet Ruth Llano
Inés Ardao
José Manuel Brea
Luz Romero
María P. Pata
Antón L. Martínez
Manuel Macía
María Isabel Loza
author_sort Ruth Llano
collection DOAJ
description Preterm delivery affects approximately 10% of pregnancies worldwide and remains a major clinical challenge due to the lack of reliable early predictive tools. Existing strategies are often invasive, relying on blood or amniotic fluid samples and requiring complex processing. In this study, we describe a novel non-invasive approach based on the multiplex detection of inflammatory cytokines in small urine volumes from pregnant women. To account for clinical and temporal variability, we applied Generalized Additive Models for Location, Scale, and Shape (GAMLSS) to adjust for gestational age at sampling and obstetric factors. Correlation network analyses revealed cytokine interactions that distinguished preterm from term deliveries, with macrophage-derived cytokines—MIP-1α, MIP-1β, IL-15, and IL-22—emerging as central nodes. These findings highlight the involvement of the IL-1 pathway in the pathophysiology of preterm labor. Furthermore, urinary IL-5 and IL-31 levels correlated positively with pregnancy duration, whereas IL-1β and IL-1Ra in urine and TNFα in amniotic fluid showed inverse associations. Altogether, this non-invasive methodology provides insight into immune dynamics during pregnancy and offers a foundation for future studies focused on biomarker discovery and mechanistic understanding of preterm birth.
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spelling doaj-art-22dea3ffaf464a5a8aef0874590bead92025-08-20T03:26:25ZengMDPI AGBiology2079-77372025-06-0114671410.3390/biology14060714Feasibility of Multiplex Cytokine Profiling in Preterm Labor: Towards Biomarker DiscoveryRuth Llano0Inés Ardao1José Manuel Brea2Luz Romero3María P. Pata4Antón L. Martínez5Manuel Macía6María Isabel Loza7Servicio de Obstetricia y Ginecología, Complejo Hospitalario Universitario de Santiago, 15706 Santiago de Compostela, SpainInnopharma Drug Screening and Pharmacogenomics Platform, BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, 15706 Santiago de Compostela, SpainHealth Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainInnopharma Drug Screening and Pharmacogenomics Platform, BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, 15706 Santiago de Compostela, SpainBiostatech Advice, Training and Innovation in Biostatistics S.L., 15895 O Milladoiro, SpainHealth Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainServicio de Obstetricia y Ginecología, Complejo Hospitalario Universitario de Santiago, 15706 Santiago de Compostela, SpainHealth Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainPreterm delivery affects approximately 10% of pregnancies worldwide and remains a major clinical challenge due to the lack of reliable early predictive tools. Existing strategies are often invasive, relying on blood or amniotic fluid samples and requiring complex processing. In this study, we describe a novel non-invasive approach based on the multiplex detection of inflammatory cytokines in small urine volumes from pregnant women. To account for clinical and temporal variability, we applied Generalized Additive Models for Location, Scale, and Shape (GAMLSS) to adjust for gestational age at sampling and obstetric factors. Correlation network analyses revealed cytokine interactions that distinguished preterm from term deliveries, with macrophage-derived cytokines—MIP-1α, MIP-1β, IL-15, and IL-22—emerging as central nodes. These findings highlight the involvement of the IL-1 pathway in the pathophysiology of preterm labor. Furthermore, urinary IL-5 and IL-31 levels correlated positively with pregnancy duration, whereas IL-1β and IL-1Ra in urine and TNFα in amniotic fluid showed inverse associations. Altogether, this non-invasive methodology provides insight into immune dynamics during pregnancy and offers a foundation for future studies focused on biomarker discovery and mechanistic understanding of preterm birth.https://www.mdpi.com/2079-7737/14/6/714preterm deliveryurinary cytokinescytokine networkinflammatory pathwaysIL-1 signalingGAMLSS
spellingShingle Ruth Llano
Inés Ardao
José Manuel Brea
Luz Romero
María P. Pata
Antón L. Martínez
Manuel Macía
María Isabel Loza
Feasibility of Multiplex Cytokine Profiling in Preterm Labor: Towards Biomarker Discovery
Biology
preterm delivery
urinary cytokines
cytokine network
inflammatory pathways
IL-1 signaling
GAMLSS
title Feasibility of Multiplex Cytokine Profiling in Preterm Labor: Towards Biomarker Discovery
title_full Feasibility of Multiplex Cytokine Profiling in Preterm Labor: Towards Biomarker Discovery
title_fullStr Feasibility of Multiplex Cytokine Profiling in Preterm Labor: Towards Biomarker Discovery
title_full_unstemmed Feasibility of Multiplex Cytokine Profiling in Preterm Labor: Towards Biomarker Discovery
title_short Feasibility of Multiplex Cytokine Profiling in Preterm Labor: Towards Biomarker Discovery
title_sort feasibility of multiplex cytokine profiling in preterm labor towards biomarker discovery
topic preterm delivery
urinary cytokines
cytokine network
inflammatory pathways
IL-1 signaling
GAMLSS
url https://www.mdpi.com/2079-7737/14/6/714
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