CITE-seq analysis reveals human cytomegalovirus and diabetes-associated adaptive NK cell alterations in cardiovascular disease

Abstract

Coronary artery disease (CAD) is a leading cause of mortality worldwide with Diabetes and human cytomegalovirus (HCMV) infection as risk factors. CAD's influence on human NK cells is not well characterized. CITE-seq analysis of a CAD cohort of 61 patients revealed distinctly higher NK cell SPON2 expression and lower IFNG expression in severe CAD patients. Interestingly, HCMV+ patients displayed lower SPON2 expression while diabetes status reversed the HCMV effect. Diabetes led to diminished adaptive FcεRIγ -/low NK cell frequencies and was associated with a higher PBMC IL15/TGFB transcript ratio, while TGFB increased in severe CAD. SPON2 expression corresponded to changes in conventional vs. adaptive NK cell frequencies, and the SPON2/IFNG ratio decreased in inflamed plaque tissue with an increased adaptive NK cell gene signature and was increased in severe CAD patients. Our results indicate that the SPON2/IFNG ratio and adaptive NK cell gene signature associated with stenosis severity or inflammation in CAD.