CITE-Seq Analysis Reveals a Differential Natural Killer Cell SPON2 Expression in Cardiovascular Disease Patients Impacted by Human-Cytomegalovirus Serostatus and Diabetes

Coronary artery disease (CAD) is linked to atherosclerosis plaque formation. In pro-inflammatory conditions, human Natural Killer (NK) cell frequencies in blood or plaque decrease; however, NK cells are underexplored in CAD pathogenesis, inflammatory mechanisms, and CAD comorbidities, such as human cytomegalovirus (HCMV) infection and diabetes. Analysis of PBMC CITE-seq data from sixty-one CAD patients revealed higher blood NK cell <i>SPON2</i> expression in CAD patients with higher stenosis severity. Conversely, NK cell <i>SPON2</i> expression was lower in pro-inflammatory atherosclerosis plaque tissue with an enriched adaptive NK cell gene signature. In CAD patients with higher stenosis severity, peripheral blood NK cell <i>SPON2</i> expression was lower in patients with high HCMV-induced adaptive NK cell frequencies and corresponded to lower PBMC <i>TGFβ</i> transcript expression with dependency on diabetes status. These results suggest that high NK cell <i>SPON2</i> expression is linked to atherosclerosis pro-homeostatic status and may have diagnostic and prognostic implications in cardiovascular disease.