Comprehensive Immune-Phenotyping of Peripheral Lymphocytes in Coronary Artery Disease Reveals Potential Roles of Effector Memory and PD-1⁺ CD4⁺ T Cells.

Chronic inflammation plays a key role in the pathogenesis of coronary artery disease (CAD), yet the peripheral immune profile in CAD remains insufficiently characterized. This study aimed to assess circulating lymphocyte subsets in CAD patients and their potential clinical relevance. Peripheral blood from 48 patients with angiographically confirmed CAD and 14 age- and sex-matched controls was analyzed using flow cytometry. A comprehensive antibody panel was used to characterize T, B, and NK cell populations. Multiple comparisons were corrected using the Benjamini–Hochberg procedure. Q values represent false discovery rate–adjusted p values. Among subsets analyzed, only effector memory (EM) CD4⁺ and PD-1⁺ CD4⁺ T cells were significantly elevated in CAD patients. EM CD4⁺ cells showed higher counts (147 vs. 102 cells/µL) and proportions (23.9% vs. 15.2%) compared to controls, and PD-1⁺ CD4⁺ cells showed similar increases (160 vs. 95 cells/µL; 23.6% vs. 13.5%). After adjusting for high-sensitivity C-reactive protein (hsCRP), both subsets remained positively correlated with monocyte counts and inversely associated with total bilirubin levels. Furthermore, EM CD4⁺ T cells showed positive associations with circulating IL-1β (r = 0.487, p < 0.001, q = 0.035) and IL-8 (r = 0.471, p < 0.001, q = 0.04) levels, whereas PD-1⁺ CD4⁺ T cells demonstrated negative associations with IL-4 (r = − 0.537, p < 0.001, q = 0.018) and IL-10 (r = − 0.522, p < 0.001, q = 0.026). In conclusion, EM and PD-1⁺ CD4⁺ T cells are selectively enriched in CAD patients and show consistent associations with monocytes, total bilirubin, and circulating cytokines independent of hsCRP, reflecting immune alterations beyond systemic inflammation.  GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10753-026-02485-8.