Changes in Cord Blood Dendritic Cells as Biomarkers of Fetal Exposure to Stressor Stimuli

DCs are central to fetal defences and it was postulated that phenotypic changes on CBDCs in response to infectious/stressor stimuli could identify compromised fetuses. Investigations were performed on whole blood using monoclonal antibody labelling and flow cytometry. Functional studies included endocytosis of Dextran particles and MLR. Both plasmacytoid (HLA-DR⁺CD11c⁻) and myeloid (HLA-DR⁺CD11c⁺) DCs were identified in CB. Additionally CB contained a DC subset with a HLA-DR⁺CD11c⁻CD45^intermediate(inm) phenotype. This population expressed lower levels of CD45 and HLA-DR and did not express plasmacytoid (CD123, BDCA2, and CD45RA) or myeloid (CD33 and CD13) markers. All subsets exhibited endocytosis and unlabelled CBDCs exhibited lymphocytic stimulatory capacity. Both myeloid and plasmacytoid CBDC subsets showed no change with gestation. The CD11c⁻ CD45^inm subset decreased with increasing gestation representing 31.33% of total DCs in preterm, 21.26% in term CB and 1.54% in adult PB. CD11c⁻CD45inm DC numbers expressing CD40, CD86 and production of IL-12 increased significantly with stressors. The myeloid and the plasmacytoid subsets showed no upregulation of CD40 and CD86 with stressors. The myeloid subset decreased while the plasmacytoid subset increased IL-12 production with stressors. Neutrophilic activation markers of CD11b and CD16 showed significant correlation with the stressed CB samples which exhibited proinflammatory DC responses, thus validating the clinical classification. These data indicate that CB contains plasmacytoid and myeloid DC populations as seen in adult PB. Additionally this study has identified a hitherto unreported CBDC subset with an immature phenotype, exhibiting endocytosis and phenotypically distinct from plasmacytoid DCs. Of the three subsets, only the CD11c⁻CD45^inm subset showed a costimulatory response to stressors suggesting this subset to be the most kinetic; changing with advancing gestation as well as exposure to stressors. Thus investigating phenotypic changes on CBDC subsets, especially on the CD11c⁻CD45^inm subset, could serve to identify fetuses exposed to stressor stimuli and at risk of adverse sequelae.Open Acces

Social prevalence of knowledge about ectopic pregnancy – tip of the ‘health inequalities’ iceberg?

We aimed to assess the social and demographic factors determining the level of awareness of the signs and symptoms of ectopic pregnancy (EP) in an East London female population and determine if awareness was related to adverse outcomes. This was a prospective, observational study using a structured questionnaire to assess awareness of EP. A retrospective analysis of a database of EP patients was used to assess the association between adverse clinical outcomes and knowledge about EP. A younger age (500 ml of blood loss were higher in the ethnic minorities. RR of >500 ml of blood loss if Asian compared to white is 1.1034 and if black compared to white is 1.1201. Blacks are more likely than whites and Asians to have blood loss >1000 ml (p = .019). An ethnic minority, a lower education level, the older age groups, those with a lower income and with non-professional careers are linked to a lower level of knowledge about EP. Ethnic minority communities have a higher risk of adverse clinical outcomes.Impact Statement What is already known on this subject? Research has identified demographic and social factors which prove that victims of health inequalities are usually the poor and the marginalised. What the results of this study add? To-date, our study is the only one to establish that the level of knowledge about ectopic pregnancy (EP) is influenced by demographic and socioeconomic factors and that lower levels of knowledge are significantly associated with adverse clinical outcomes. Our findings show that ethnic minority women are more likely to suffer morbidity from EP than their Caucasian counterparts. We have also established that women of poorer backgrounds, women with lesser levels of education and in non-professional jobs are least likely to be aware of signs and symptoms and consequences of EP. What the implications are of these findings for clinical practice and/or further research? The health service has a responsibility to identify these populations and target them for interventions to correct these health inequalities. We propose a multifaceted plan to increase the level of knowledge of these identified sections of the local community