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Observational Study
. 2014 Dec;211(6):678.e1-12.
doi: 10.1016/j.ajog.2014.06.035. Epub 2014 Jun 19.

Maternal serum serpin B7 is associated with early spontaneous preterm birth

Samuel Parry  1 , Heping Zhang  2 , Joseph Biggio  3 , Radek Bukowski  4 , Michael Varner  5 , Yaji Xu  2 , William W Andrews  3 , George R Saade  4 , M Sean Esplin  5 , Rita Leite  6 , John Ilekis  7 , Uma M Reddy  7 , Yoel Sadovsky  8 , Ian A Blair  9 ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Genomic and Proteomic Network for Preterm Birth Research
Collaborators, Affiliations
Observational Study

Maternal serum serpin B7 is associated with early spontaneous preterm birth

Samuel Parry et al. Am J Obstet Gynecol. 2014 Dec.

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.

Keywords: preterm birth; proteomics; serine proteinase inhibitors.

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Figures

Figure 1
Figure 1
Protocols for targeted (1A) and shotgun (1B) proteomics comparing pooled maternal serum samples from five spontaneous preterm births and five term deliveries.
Figure 1
Figure 1
Protocols for targeted (1A) and shotgun (1B) proteomics comparing pooled maternal serum samples from five spontaneous preterm births and five term deliveries.
Figure 2
Figure 2
Protocol for comparing the levels of 31 candidate proteins by liquid chromatography-multiple reaction monitoring mass spectrometry in individual maternal serum samples from nested preterm birth cases and controls.
Figure 3
Figure 3
Flow chart of patients in the longitudinal cohort whose serum samples from second and third study visits were used in proteomic analyses. SPTB = spontaneous preterm birth.
Figure 4
Figure 4
Western blots demonstrating serpin B7 and beta-tubulin (loading control) expression in representative amnion, chorion, and placenta samples. The blots were probed for serpin B7 expression using a rabbit polyclonal antibody to a 330-amino acid peptide of human serpin B7 (ab47740, Abcam). Samples were mixed in each gel to enhance objectivity of assessment. TD = term delivery. PTD = preterm delivery.
Figure 5
Figure 5
Bar graphs demonstrating serpin B7 expression (normalized to beta-tubulin expression) in amnion, chorion, and placenta samples from preterm deliveries (PTD) and term deliveries (TD), +/− labor preceding delivery.
See this image and copyright information in PMC

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