Maternal serum serpin B7 is associated with early spontaneous preterm birth - 25/07/14

Doi : 10.1016/j.ajog.2014.06.035

Samuel Parry, MD ^a,^⁎ , Heping Zhang, PhD ^b, Joseph Biggio, MD ^c, Radek Bukowski, MD, PhD ^d, Michael Varner, MD ^e, Yaji Xu, PhD ^b, William W. Andrews, MD, PhD ^c, George R. Saade, MD ^d, M. Sean Esplin, MD ^e, Rita Leite, MD ^a, John Ilekis, PhD ^f, Uma M. Reddy, MD, MPH ^f, Yoel Sadovsky, MD ^g, Ian A. Blair, PhD ^h
for the
Eunice Kennedy Shriver National Institute of Child Health and Human Development Genomic and Proteomic Network for Preterm Birth Research
^a Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA
^b Department of Biostatistics, Yale University School of Public Health, New Haven, CT
^c Department of Obstetrics and Gynecology, University of Alabama, Birmingham, School of Medicine, Birmingham, AL
^d Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX
^e Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT
^f Pregnancy and Perinatology Branch, Center for Developmental Biology and Perinatal Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD
^g Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA
^h Center for Cancer Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA

^∗Corresponding author: Samuel Parry, MD.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Friday 25 July 2014
Cet article a été publié dans un numéro de la revue, cliquez ici pour y accéder

Abstract

Objective

We sought to identify serum biomarkers of early spontaneous preterm birth (SPTB) using semiquantitative proteomic analyses.

Study Design

This was a nested case-control study of pregnant women with previous SPTB. Maternal serum was collected at 19-24 and 28-32 weeks’ gestation, and analyzed by liquid chromatography-multiple reaction monitoring/mass spectrometry. Targeted and shotgun proteomics identified 31 candidate proteins that were differentially expressed in pooled serum samples from spontaneous preterm (cases [<34 weeks]) and term (controls) deliveries. Candidate protein expression was compared in individual serum samples between cases and controls matched by age and race groups, and clinical site. Protein expression was verified by Western blot in the placenta and fetal membranes from cases and controls.

Results

Serum samples were available for 35 cases and 35 controls at 19-24 weeks, and 16 cases and 16 controls at 28-32 weeks. One protein, serpin B7, yielded serum concentrations that differed between cases and controls. The mean concentration of serpin B7 at 28-32 weeks was 1.5-fold higher in women with subsequent preterm deliveries compared to controls; there was no difference at 19-24 weeks. Higher levels of serpin B7 at both gestational age windows were associated with a shorter interval to delivery, and higher levels of serpin B7 in samples from 28-32 weeks were associated with a lower gestational age at delivery. Western blotting identified serpin B7 protein in placenta, amnion, and chorion from cases and controls.

Conclusion

Targeted and shotgun serum proteomics analyses associated 1 protein, serpin B7, with early SPTB. Our results require validation in other cohorts and analysis of the possible mechanistic role of serpin B7 in parturition.

Le texte complet de cet article est disponible en PDF.

Key words : preterm birth, proteomics, serine proteinase inhibitors

Plan

Materials and Methods

Longitudinal cohort

Proteomics techniques

	This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Genomic and Proteomic Network for Preterm Birth Research, grant numbers U01-HD-050062, U01-HD-050078, U01-HD-050080, U01-HD-050088, and U01-HD-050094.
	The authors report no conflict of interest.
	Cite this article as: Parry S, Zhang H, Biggio J, et al. Maternal serum serpin B7 is associated with early spontaneous preterm birth. Am J Obstet Gynecol 2014;211:x.ex-x.ex.