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

Abstract

AbstractCoronary 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 cellSPON2expression and lowerIFNGexpression in severe CAD patients. Interestingly, HCMV+patients displayed lowerSPON2ex-pression while diabetes status reversed the HCMV effect. Diabetes led to diminished adaptive FcεRIγ−/lowNK cell frequencies and was associated with a higher PBMCIL15/TGFBtranscript ratio, while TGFB in-creased in severe CAD.SPON2expression corresponded to changes in conventional vs. adaptive NK cell frequencies, andSPON2/IFNGratio decreased in inflamed plaque tissue with an increased adaptive NK cell gene signature and was increased in severe CAD patients. Our results indicate that theSPON2/IFNGra-tio and adaptive NK cell gene signature associated with stenosis severity or inflammation in CAD.