Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Increased Macrophage-Specific Arterial Infiltration Relates to Non-calcified Plaque and Systemic Immune Activation in People with HIV.

Abstract

BACKGROUND: Persistent immune activation is thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with HIV (PWH). METHODS: Participants (>=18 years) with versus without HIV and without history of clinical ASCVD were enrolled. We hypothesized that increased macrophage-specific arterial infiltration would relate to plaque composition and systemic immune activation among PWH. We applied a novel targeted molecular imaging approach [technetium-99 m (99mTc)-tilmanocept single photon emission computed tomography (SPECT)/CT] and comprehensive immune phenotyping. RESULTS: Aortic 99mTc-tilmanocept uptake was significantly higher among PWH (N = 20) versus participants without HIV (N = 10) with similar 10-year ASCVD risk (P = 0.02). Among PWH, but not among participants without HIV, non-calcified aortic plaque volume related directly to aortic 99mTc-tilmanocept uptake at different uptake thresholds. An interaction (P = 0.001) was seen between HIV status and non-calcified plaque volume, but not calcified plaque (P = 0.83). Systemic levels of caspase-1 (P = 0.004), CD14-CD16+ (non-classical/patrolling/homing) monocytes (P = 0.0004) and CD8+ T-cells (P = 0.005) related positively and CD4+/CD8 + T-cell ratio (P = 0.02) inversely to aortic 99mTc-tilmanocept uptake volume. CONCLUSIONS: Macrophage-specific arterial infiltration was higher among PWH and related to non-calcified aortic plaque volume only among PWH. Key systemic markers of immune activation relating to macrophage-specific arterial infiltration may contribute to heightened ASCVD risk among PWH.