UNCOVERING ASSOCIATIONS BETWEEN BLOOD PRESSURE PHENOTYPES AND IMMUNE TRAITS IN TWINSUK

Abstract

Objective: The primary aim of this work was to define the contribution of both the innate and adaptive immune system arms to blood pressure changes. Design and method: In order to define the inter-relationships between immune cell subtypes, blood pressure (BP) and susceptibility to hypertension (HT), we carried out association analyses between 23,394 immune phenotypes and blood pressure measures [systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP)] and HT. After calculating the mean SBP and DBP values from two BP measurements, we adjusted for medication use by adding 15- and 10-mm Hg to SBP and DBP respectively for individuals reported to be on BP-lowering treatment. PP was calculated as SBP minus DBP according to medication adjusted traits. HT was defined as (i) SBP>=140 mm Hg, (ii) DBP>=90 mm Hg or taking BP-lowering medication. We undertook a comprehensive and high-resolution deep immunophenotyping flow-cytometry approach, to examine immune traits in 502 female twins from TwinsUK. The platform used covered all major lymphocyte and myeloid subsets in peripheral blood. A linear/logistic mixed model regression analysis adjusted for family structure, age and BMI was used to examine the associations between immune traits and blood pressure phenotypes and HT status respectively. Results: We observed statistically significant associations (Bonferroni P-value < 1.71x10–4) between blood pressure phenotypes and immune cell subtypes. In particular, DBP showed 47 significant associations with distinct myeloid cell types of CD8 differentiation T cells. SBP showed 59 significant associations with both CD8 differentiation T cells and specific myeloid subpopulations such as monocytes. PP showed 4 significant associations with monocyte subpopulations. Analysis of HT revealed 7 associations with monocytes, CD8 T cells and dendritic cells. Conclusions: The results reported in this study provide preliminary evidence of an inter-relationship between blood pressure and human immune cell profile associations. We have shown for the first time that change in the proportions of immune cells correlates with blood pressure measurements.