CD38 ⁺ T-Cell Count Is an Immunologic Phenotype Associated With Blood Pressure

BACKGROUND: T lymphocytes play a crucial role in the development of hypertension and associated end-organ damage. CD38 is a well-established surface marker for T-cell activation. However, clinical evidence linking CD38 + T cells, or other specific T-cell subsets, with blood pressure (BP) changes remains limited. We therefore sought to determine whether CD38 + T-cell abundance correlates with BP and whether anti-CD38 therapy influences BP in humans and mice. METHODS: We performed correlation analyses between peripheral immune cell counts and BP in 197 normotensive and 53 hypertensive subjects. The impact of CD38-targeted therapy on BP was evaluated in multiple myeloma patients (control, n=50; daratumumab, n=27). In addition, we used a murine model of angiotensin II–induced hypertension to characterize T-cell frequency and phenotype in the circulation and kidney by flow cytometry. RESULTS: Circulating CD38 + T-cell abundance was inversely correlated with BP in both normotensive and hypertensive subjects. This finding was recapitulated in hypertensive mice, which also showed concomitant accumulation of CD38 + T cells in the kidney. In patients, daratumumab-induced depletion of CD38 + cells reduced systolic BP by ≈10 mm Hg for 4 to 6 weeks. This BP-lowering effect was similarly observed in hypertensive mice given an antimurine CD38 antibody. CONCLUSIONS: Our data identify circulating CD38 + T cells as a novel immunologic biomarker that inversely correlates with BP, potentially reflecting T-cell transmigration during BP elevation.