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Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis
Tomas Raul Wiche Salinas1,2, Yuwei Zhang1,2, Annie Gosselin2
1Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal (UdeM), Montreal, QC H2X 0A9, Canada.
Insights
Cardiovascular disease (CVD) risk in people with HIV (PLWH) on antiretroviral therapy (ART) is linked to low Th17 cells and abundant non-classical monocytes. These immune changes correlate with subclinical coronary artery atherosclerosis (CAA).
Area of Science:
- Immunology
- Cardiology
- Infectious Diseases (HIV/AIDS)
Background:
- Cardiovascular disease (CVD) is a significant comorbidity in people living with HIV-1 (PLWH) undergoing antiretroviral therapy (ART).
- Previous research indicated increased coronary artery atherosclerosis (CAA) plaque burden in ART-treated PLWH compared to uninfected individuals.
Purpose of the Study:
- To identify novel immunological correlates of subclinical coronary artery atherosclerosis (CAA) in ART-treated PLWH.
- To investigate the relationship between markers of intestinal damage, inflammation, specific T-cell subsets, monocytes, and dendritic cells with CAA.
Main Methods:
- Analysis of plasma markers (sCD14, LBP, FABP2, CCL20, CX3CL1, MIF, CCL25), T-cell subsets (Th17, Tregs), monocyte subsets, and dendritic cells.
- Correlation of these markers with coronary artery atherosclerosis (CAA) plaque volume (TPV/LAPV) measured by CTAScan.
- Logistic regression analysis adjusted for Framingham Risk Score (FRS) and HIV/ART duration.
Main Results:
- TPV detection was associated with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1, triglycerides, and classical monocyte expansion; and lower Th17/Treg ratios.
- ART-treated PLWH with CAA (TPV+) showed lower Th17 frequencies, reduced Th17/Treg ratios, higher non-classical CCR9lowHLADRhigh monocyte frequencies, and increased fibrinogen.
- Th17/Treg ratios and non-classical monocyte frequencies remained significant predictors of TPV/LAPV after adjustment.
Conclusions:
- Paucity of Th17 cells and abundance of non-classical monocytes are novel immunological correlates of subclinical coronary artery atherosclerosis (CAA).
- These immune alterations may contribute to the elevated cardiovascular disease (CVD) risk observed in ART-treated PLWH.
Abstract:
Cardiovascular disease (CVD) remains an important comorbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed in the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) > 5%) revealed a 2-3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by computed tomography angiography scan (CTAScan) as the total (TPV) and low attenuated plaque volume (LAPV), in ART-treated PLWH (HIV+) versus uninfected controls (HIV-). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4+ T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1, and triglyceride levels; lower Th17/Treg ratios; and classical monocyte expansion. Among HIV+, TPV+ versus TPV- exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9lowHLADRhigh monocytes, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9lowHLADRhigh monocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.
