Abstract Coronary artery disease (CAD) is a leading cause of mortality worldwide with Diabetes and human cyto-megalovirus (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 ex-pression 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 in-creased in severe CAD. SPON2 expression corresponded to changes in conventional vs. adaptive NK cell frequencies, and 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 ra-tio and adaptive NK cell gene signature associated with stenosis severity or inflammation in CAD.

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