Abstract P251: Circulating Immune Cell Phenotypes Are Associated With Inflammatory Biomarkers in the Framingham Heart Study Offspring Cohort

Abstract

Age-related changes in circulating immune cells have been associated with inflammation and immunosenescence, increasing susceptibility to cardiovascular disease. This study investigated the association between circulating immune cell phenotypes and inflammatory biomarkers in the Framingham Heart Study Offspring cohort. Participants (N=865, 52% female, mean age 62) were immunophenotyped using peripheral blood mononuclear cells with 37 immune cell phenotypes and 6 composite ratio measures, including T cells, B cells, NK cells, and monocytes. The inflammatory biomarkers were profiled in plasma samples using the OLINK Proteomics inflammation panel. Pairwise cross-sectional associations between 43 circulating immune cell phenotypes and 68 protein biomarkers were investigated using linear mixed-effect models accommodating familial correlations and adjusting for covariates (sex, age, number of apolipoprotein E ( APOE) ε2 and ε4 alleles, and cytomegalovirus levels), with FDR ≤0.05 to declare significant associations. Age-stratified analyses were performed to explore effect modification. CD8 T naïve cells (CD8Tn) were negatively associated with several proteins ( Figure ). Significant associations were also observed for CD4 T cell subtypes including higher levels of CD4 T helper cells associated with lower Flt3L and TNFRSF9, higher levels of CD4 T central memory (Tcm) and CD4 T effector (Teff) cells associated with lower TNFB, and higher CD4 Teff associated with lower CD40 levels. Among associations identified in the full sample, we observed a large proportion of associations between CD4 T cell subtypes and CD8 Tn in the older age group (>60 years) but not the younger age group. Our results suggest that people tend to have more inflammation-associated immune responses during aging. Future studies are needed to improve understanding of the contribution of these inflammation-immune cell associations to cardiovascular disease.