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Title: Cervical antimicrobial immunity in pregnancy
Author: James, C. P.
ISNI:       0000 0004 7659 8117
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2015
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Preterm birth (PTB) is a major problem in the UK and worldwide, leading to high mortality and significant long-term morbidity. A complex interaction between ascending genital tract infection and the maternal immune system is the likely underlying pathogenesis. We hypothesized that impaired cervical immunity leads to ascending infection and PTB i.e. women at high risk of PTB have a distinct cervical innate immune phenotype, which reflects genotypic variance. The systemic and mucosal expression and function of human beta defensins (HBDs), antimicrobial peptides with a range of immunomodulatory properties were investigated. The study included: (1) a comprehensive antenatal survey of lower genital tract (LGT) infections and dysbiosis in women at increased risk of PTB; (2) a case control study, investigating the relationship between HBD genotype and PTB; (3) an observational study investigating the relationship between cervical innate immune phenotype and (a) the risk of PTB and (b) HBD genotype; and (4) an in vitro investigation to examine endocervical HBD expression in response to progesterone. The prevalence of sexually transmitted LGT infections was low in this cohort of women at increased risk of PTB. Bacteria associated with vaginal dysbiosis and chorioamnionitis were more prevalent, and antenatal Group B streptococcus or Peptostreptococcus micros carriage were associated with both altered antimicrobial immunity and PTB. HBD expression varied systemically and in the cervix according to genotype, and the cervicovaginal antimicrobial killing activity correlated with both HBD protein levels and genotype in women who delivered at term. The relationship between HBD genotype and protein expression was altered in women who delivered preterm; increased cervicovaginal HBD1 levels were associated with PTB. These findings suggest that women who deliver preterm have altered cervicovaginal antimicrobial immunity, which may contribute to the pathogenesis of infection related PTB.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available