elafin and Premature-Birth

Bacterial vaginosis due to Gardnerella vaginalis (GV) is one of the main causes of preterm birth. Antimicrobial function of the cervical glands prevents ascending pathogen infection. This study investigated the effect of GV on the cervical gland cells. We examined the correlation between GV and neutrophil elastase in the cervical mucous obtained from pregnant women's clinical samples. Culture supernatants (sup) of GV and Lactobacillus crispatus (LC) were added to human immortalized cervical gland cells (EndoCx). Quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine the effects on the production of antimicrobial peptides (AMPs), secretory leukocyte peptidase inhibitor (SLPI), and Elafin. mRNA microarray analysis revealed the expression profile of GV-exposed EndoCx. Moreover, the antimicrobial activity of Elafin against LC and GV was investigated. In the clinical samples, neutrophil elastase was increased in the GV-positive cervical mucous. In an in vitro assay, RT-qPCR and ELISA showed that GV-sup enhanced the secretion of Elafin, but not SLPI, from EndoCx, whereas LC-sup did not. mRNA microarray assay and ELISA results demonstrated that GV-sup enhanced the proinflammatory pathway and interleukin (IL)- 8 secretion from EndoCx as well as cell adhesion and tight junction pathways. Moreover, GV-sup directly enhanced Elafin and IL-8 secretion from the cervical gland cells. In the GV-abundant vaginal flora, IL-8 level increased the neutrophil elastase activity and Elafin inhibited the elastase activity to protect from tissue damage and infection. Thus, the balance of IL-8-induced neutrophil and Elafin-induced antiprotease activities may be crucial in preterm labor.

Topics: Antimicrobial Peptides; Elafin; Epithelium; Female; Gardnerella vaginalis; Humans; Infant, Newborn; Interleukin-8; Leukocyte Elastase; Pregnancy; Premature Birth; RNA, Messenger; Secretory Leukocyte Peptidase Inhibitor

To evaluate trappin-2 levels in cervicovaginal secretions for prediction of spontaneous preterm birth (sPTB) and compare it with transvaginal sonography (TVS) cervical length in asymptomatic women at risk of PTB.. Trappin-2 levels assessed in cervicovaginal secretions collected from 80 asymptomatic pregnant women at high risk for preterm delivery and cervical length measured by TVS, first at 14-20 weeks of pregnancy and repeated 8 weeks later. On the basis of delivery outcomes, participants were divided into cases (delivery <37 weeks) and controls (delivery at 37-41 weeks).. The mean value of cervicovaginal trappin-2 was significantly higher in women who delivered preterm (n = 40), compared with the term group (n = 40: P < 0.001) both at 14-20 weeks and at 22-28 weeks. The critical cut-off value for cervicovaginal trappin-2 at 14-20 weeks was 4620 pg/mL, above which participants delivered prematurely with sensitivity, specificity, and positive and negative predictive values of 82.5%, 71.0%, 78.5%, and 81.5% respectively, whereas TVS cervical length in this window period was not significantly associated with preterm birth. At 22-28 weeks a trappin-2 value of 6900 pg/mL had similar predictive accuracy.. Raised cervicovaginal trappin-2 levels can be used as an early tool for prediction of PTB as early as 14-20 weeks (earlier than TVS) in asymptomatic high-risk women.

Topics: Adult; Body Fluids; Case-Control Studies; Cervical Length Measurement; Cervix Uteri; Elafin; Female; Humans; Infant, Newborn; Predictive Value of Tests; Pregnancy; Premature Birth; Ultrasonography; Young Adult

There is much interest in the role of innate immune system proteins (antimicrobial peptides) in the inflammatory process associated with spontaneous preterm birth (sPTB). After promising pilot work, we aimed to validate the association between the antimicrobial peptides/proteins elafin and cathelicidin and sPTB. An observational cohort study of 405 women at high-risk, and 214 women at low-risk of sPTB. Protein concentrations of elafin and cathelicidin, and the enzyme human neutrophil elastase (HNE) were measured in over 1,000 cervicovaginal fluid (CVF) samples (10 to 24 weeks' gestation). Adjusted CVF cathelicidin and HNE concentrations (but not elafin) were raised in high-risk women who developed cervical shortening and who delivered prematurely and were predictive of sPTB < 37 weeks, with an area under the curve (AUC) of 0.75 (95% CI 0.68 to 0.81) for cathelicidin concentration at 14 to 15

Topics: Adult; Antimicrobial Cationic Peptides; Body Fluids; Case-Control Studies; Cathelicidins; Cervix Uteri; Cohort Studies; Elafin; Female; Gestational Age; Humans; Immunity, Innate; Leukocyte Elastase; Pore Forming Cytotoxic Proteins; Pregnancy; Premature Birth; Prospective Studies; Risk Factors; Vagina

Early spontaneous preterm birth is associated with inflammation/infection and shortening of the cervix. We hypothesised that cervico-vaginal production of trappin2/elafin (peptidase inhibitor 3) and cathelicidin antimicrobial peptide (cathelicidin), key components of the innate immune system, are altered in women who have a spontaneous preterm birth. The aim was to determine the relationship between cervico-vaginal fluid (CVF) trappin2/elafin and cathelicidin protein concentrations with cervical length in woman at risk of spontaneous preterm birth. Trappin2/elafin and cathelicidin were measured using ELISA in longitudinal CVF samples (taken between 13 to 30 weeks' gestation) from 74 asymptomatic high risk women (based on obstetric history) recruited prospectively. Thirty six women developed a short cervix (<25 mm) by 24 weeks' and 38 women did not. Women who developed a short cervix had 2.71 times higher concentrations of CVF trappin2/elafin from 14 weeks' versus those who did not (CI 1.94-3.79, p<0.0005). CVF trappin2/elafin before 24 weeks' was 1.79 times higher in women who had a spontaneous preterm birth <37 weeks' (CI: 1.05-3.05, p = 0.034). Trappin2/elafin (>200 ng/ml) measured between 14+0-14+6 weeks' of pregnancy predicted women who subsequently developed a short cervix (n = 11, ROC area = 1.00, p = 0.008) within 8 weeks. Cathelicidin was not predictive of spontaneous delivery. Vitamin D status did not correlate with CVF antimicrobial peptide concentrations. Raised CVF trappin2/elafin has potential as an early pregnancy test for prediction of cervical shortening and spontaneous preterm birth. This justifies validation in a larger cohort.

Topics: Adult; Antimicrobial Cationic Peptides; Biomarkers; Cathelicidins; Cervix Uteri; Elafin; Female; Humans; Pregnancy; Premature Birth; Uterine Cervical Diseases; Vitamin D