Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants
2.2. Computed Tomography Angiography Scan
2.3. ELISA
2.4. Flow Cytometry
2.5. Statistical Analysis
3. Results
3.1. Laboratory and Imaging Markers of Subclinical Atherosclerosis in ART-Treated PLWH
3.2. Plasma Markers in Relationship with HIV-1 Status and Subclinical Atherosclerosis
3.3. T-Cell Profile Alterations in Relationship with HIV-1 Status and Subclinical Atherosclerosis
3.4. Monocyte Alterations in Relationship with HIV-1 Status and Subclinical Atherosclerosis
3.5. mDC and pDC Frequencies in Relationship with HIV-1 Status and Subclinical Atherosclerosis
3.6. Multivariate Analysis Identifies an Immunological Signature Associated with Subclinical Atherosclerosis in ART-Treated PLWH
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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HIV+ (n = 61) | HIV− (n = 21) | p-Value | |
---|---|---|---|
Demographics and Clinical Information | |||
Age (years) * | 55.38 ± 6.99 | 56.94 ± 7.99 | 0.39 |
Male & | 61 (100%) | 17 (81%) | 0.003 |
BMI (kg/m2) # | 24.43 (22.10–28.29) | 25.72 (24.34–28.33) | 0.2023 |
Framingham Risk Score (FRS) # | 10 (6–14.25) | 8 (8–12.5) | 0.67 |
Current Statin Treatment & | 14 (23%) | 5 (23.8%) | 1 |
Smoking & | 0.502 | ||
Never | 18 (29.5%) | 8 (38.1%) | |
Current Smoker | 23 (37.7%) | 5 (23.8%) | |
Former Smoker | 20 (32.8%) | 8 (38.1%) | |
Coronary Artery Disease Parameters | |||
Total Plaque Volume (TPV; mm3) # | 108.30 (0–698) | 49.70 (0–279.1) | 0.32 |
Low Attenuated Plaque Volume (LAPV; mm3) # | 34.40 (0–194.5) | 10.53 (0–118.9) | 0.39 |
Laboratory Parameters | |||
White Blood Cells (×109/L) # | 5.6 (4.7–7.1) | 6.15 (5.65–7) | 0.2580 |
Lymphocytes (×109/L) * | 1.90 ± 0.66 | 1.87 ± 0.47 | 0.85 |
LDL (mmol/L) # | 2.58 (2.13–3.40) | 3.10 (2.30–3.82) | 0.21 |
HDL (mmol/L) # | 1.23 (1.07–1.3) | 1.44 (1.30–1.6) | 0.002 |
Triglycerides (mmol/L) # | 1.73 (1.19–2.99) | 1.21 (0.89–1.68) | 0.008 |
TPV+ (n = 39) | TPV− (n = 22) | p-Value | |
---|---|---|---|
Demographics and Clinical Parameters | |||
Age (years) * | 56.24 ± 6.35 | 53.85 ± 7.93 | 0.1625 |
Male & | 39 (100%) | 22 (100%) | NA |
BMI (kg/m2) # | 24.05 (21.05–28.38) | 25.29 (22.91–28.27) | 0.23 |
Framingham Risk Score # | 11.00 (7–18) | 8.00 (5.5–13) | 0.085 |
Current Statin Treatment & | 12 (30.8%) | 2 (9.1%) | 0.064 |
Smoking & | 0.005 | ||
Never | 7 (17.9%) | 11 (50%) | |
Current Smoker | 20 (51.3%) | 3 (13.6%) | |
Former Smoker | 12 (30.8%) | 8 (36.4%) | |
Coronary Artery Disease Parameters | |||
Total Plaque Volume (mm3) # | 608.70 (142.6–881.8) | 0 | NA |
Low Attenuated Plaque Volume (mm3) # | 164.80 (36–296) | 0 | NA |
HIV Disease Parameters | |||
Undetectable Viral Load & | 37 (94.8%) | 19 (86.36%) | 0.34 |
Duration of HIV (years) # | 19.16 (14.29–24.4) | 14.71 (4.58–24.14) | 0.06 |
Duration of ART (years) * | 16.14 ± 5.68 | 10.69 ± 7.82 | 0.003 |
Antecedent/Current Protease Inhibitor Use & | 39 (100%) | 14 (63.64%) | <0.0001 |
Nadir CD4 (×109/L) # | 195 (100–330) | 170 (78–255) | 0.397 |
Laboratory Parameters | |||
White Blood Cells (×109/L) # | 5.90 (4.7–7.8) | 5.40 (4.3–6.85) | 0.27 |
Lymphocytes (×109/L) * | 1.91 ± 0.60 | 1.89 ± 0.78 | 0.924 |
D-Dimer (ug/L) # | 300.00 (197.5–410) | 290.00 (175–380) | 0.52 |
Fibrinogen (G/L) # | 3.23 (2.73–3.78) | 2.67 (2.27–3) | 0.005 |
LDL (mmol/L) # | 2.40 (1.99–3.48) | 2.90 (2.23–3.40) | 0.35 |
HDL (mmol/L) # | 1.21 (1.07–1.37) | 1.25 (0.98–1.37) | 0.96 |
Triglycerides (mmol/L) # | 2.07 (1.26–3.1) | 1.38 (1.09–2.03) | 0.109 |
Serology | |||
Co-Infection CMV # | 36 (92.3%) | 17 (77.3%) | 0.39 |
Models | OR | Memory Th17/Treg Ratio | EM Th17/Treg Ratio | CM Th17/Treg Ratio | CCR9+ HLA-DRlow Non-Classical Monocytes | CCR9low HLA-DRhigh Non-Classical Monocytes | M-DC8+ HLA-DRhigh Monocytes |
---|---|---|---|---|---|---|---|
Crude Model | OR (CI) | 0.49 (0.27–0.86) | 0.44 (0.24–0.79) | 0.57 (0.33–0.99) | 0.30 (0.15–0.63) | 3.56 (1.45–8.74) | 2.71 (1.24–5.91) |
Adj. p | 0.03 | 0.03 | 0.05 | 0.01 | 0.02 | 0.10 | |
Model 1 | OR (CI) | 0.47 (0.22–1.02) | 0.43 (0.18–1.03) | 0.55 (0.27–1.11) | 0.24 (0.09–0.62) | 6 (1.77–20.28) | 5.39 (1.56–18.6) |
Adj. p | 0.1 | 0.1 | 0.1 | 0.015 | 0.015 | 0.04 | |
%Δ OR | 3% | 2% | 4% | 22% | 70% | 98% | |
Model 2 | OR (CI) | 0.45 (0.21–0.94) | 0.41 (0.18–0.94) | 0.52 (0.26–1.03) | 0.2 (0.07–0.56) | 6.44 (1.89–21.95) | 6.06 (1.68–21.93) |
Adj. p | 0.07 | 0.07 | 0.07 | 0.01 | 0.01 | 0.03 | |
%Δ OR | 9% | 6% | 9% | 35% | 80% | 123% | |
Model 3 | OR (CI) | 0.41 (0.19–0.91) | 0.38 (0.16–0.94) | 0.48 (0.24–0.97) | 0.17 (0.06–0.52) | 8.09 (2.06–31.67) | 7.13 (1.8–28.22) |
Adj. p | 0.06 | 0.06 | 0.06 | 0.01 | 0.01 | 0.03 | |
%Δ OR | 17% | 13% | 16% | 44% | 126% | 162% | |
Model 4 | OR (CI) | 0.45 (0.23–0.89) | 0.47 (0.24–0.92) | 0.49 (0.26–0.94) | 0.26 (0.11–0.6) | 5 (1.72–14.56) | 3.75 (1.4–10.04) |
Adj. p | 0.05 | 0.05 | 0.05 | 0.01 | 0.01 | 0.05 | |
%Δ OR | 7% | 6% | 14% | 15% | 40% | 40% | |
Model 5 | OR (CI) | 0.45 (0.24–0.86) | 0.45 (0.23–0.87) | 0.5 (0.27–0.94) | 0.26 (0.11–0.62) | 3.07 (1.14–8.25) | 2.75 (1.12–6.74) |
Adj. p | 0.04 | 0.04 | 0.04 | 0.02 | 0.1 | 0.15 | |
%Δ OR | 8% | 3% | 13% | 13% | 14% | 1% |
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Wiche Salinas, T.R.; Zhang, Y.; Gosselin, A.; Rosario, N.F.; El-Far, M.; Filali-Mouhim, A.; Routy, J.-P.; Chartrand-Lefebvre, C.; Landay, A.L.; Durand, M.; et al. Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection. Cells 2024, 13, 157. https://doi.org/10.3390/cells13020157
Wiche Salinas TR, Zhang Y, Gosselin A, Rosario NF, El-Far M, Filali-Mouhim A, Routy J-P, Chartrand-Lefebvre C, Landay AL, Durand M, et al. Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection. Cells. 2024; 13(2):157. https://doi.org/10.3390/cells13020157
Chicago/Turabian StyleWiche Salinas, Tomas Raul, Yuwei Zhang, Annie Gosselin, Natalia Fonseca Rosario, Mohamed El-Far, Ali Filali-Mouhim, Jean-Pierre Routy, Carl Chartrand-Lefebvre, Alan L. Landay, Madeleine Durand, and et al. 2024. "Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection" Cells 13, no. 2: 157. https://doi.org/10.3390/cells13020157
APA StyleWiche Salinas, T. R., Zhang, Y., Gosselin, A., Rosario, N. F., El-Far, M., Filali-Mouhim, A., Routy, J.-P., Chartrand-Lefebvre, C., Landay, A. L., Durand, M., Tremblay, C. L., & Ancuta, P., on behalf of the Canadian HIV and Aging Cohort Study (CHACS). (2024). Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection. Cells, 13(2), 157. https://doi.org/10.3390/cells13020157