Maternal serum serpin B7 is associated with early spontaneous preterm birth

Abstract

Objective To identify serum biomarkers of early spontaneous preterm birth (SPTB) using semi-quantitative proteomic analyses. Study Design Nested case-control study of pregnant women with previous SPTB. Maternal serum was collected at 19 to 24 and 28 to 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 (<34 weeks - cases) and term deliveries (controls). 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 to 24 weeks, and 16 cases and 16 controls at 28 to 32 weeks. One protein, serpin B7, yielded serum concentrations that differed between cases and controls. The mean concentration of serpin B7 at 28 to 32 weeks was 1.5-fold higher in women with subsequent preterm deliveries compared to controls; there was no difference at 19 to 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 to 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 one 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.

Protein Profiling of Women with Spontaneous Preterm Birth

“…Patients with SPTB also had high levels of INFG, this result being consistent with the findings of Curry et al 2008 in which high levels of INFG was observed in the PTB group [9] . High levels of MCP-3 were found in patients with PTB, this confirms the report by other studies in which the protein levels differ between the preterm and term in maternal plasma [16,17,22] . A high level of fractalkine was reported in pregnancy complicated with chorioamnionitis [23] .…”

“…Furthermore, animal research of anti-TNFA therapy has been shown to decrease foetal deaths and preterm deliveries in LPS-induced model of PTB [19] . In our samples, high levels of IL16, INFG, MCP-3, IL17, and fractalkine were seen among women with SPTB, which is similar to other reports in different ethnic groups [9,[16][17][18][19][20][21][22][23][24] . Patients with SPTB also had high levels of INFG, this result being consistent with the findings of Curry et al 2008 in which high levels of INFG was observed in the PTB group [9] .…”

“…High levels of cytokines can promote preterm labour by triggering preterm contractions and encouraging cervical ripening [13][14][15] . Menon and colleagues in 2008 showed that a high concentration of TNF-α in samples of AfricanAmerican women contributed to a high incidence of PTB among these women as compared to the Caucasians who were shown to have low levels of TNF-α and relatively low incidence of PTB [16][17][18] . Furthermore, animal research of anti-TNFA therapy has been shown to decrease foetal deaths and preterm deliveries in LPS-induced model of PTB [19] .…”

“…Ito and group in 2010 reported a high level of IL17 alpha in preterm delivery, which is also consistent with our findings, in which IL17 alpha was high among women with a preterm delivery [24] . Cytokines have been shown to confer ethnic disparity [6,16,17] . Malaysia is a multiethnic country consisting of three main races; namely Malay, Chinese, and Indians.…”

Use of proteomic analysis in obstetrics: First results of investigations

“…Концентрация одного из белков, серпина В7 -в пробах сыворотки, взятой в срок 28-32 нед, была выше в среднем в 1,5 раза у женщин с последующими СПР по сравнению с контрольным вариантом. Единственного ис-следования для оценки негативного последствия повы-шенной концентрации серпина В7 в сыворотке крови бе-ременных недостаточно, и целесообразна проверка полу-ченных результатов на больших выборках [20]. Интересна работа M. Esplin и соавт.…”