TY - JOUR
T1 - Interleukin-17A is associated with flow-mediated dilation and interleukin-4 with carotid plaque in persons with HIV
AU - Wanjalla, Celestine N.
AU - Temu, Tecla M.
AU - Mashayekhi, Mona
AU - Warren, Christian M.
AU - Shepherd, Bryan E.
AU - Gangula, Rama
AU - Fuseini, Hubaida
AU - Bailin, Samuel
AU - Gabriel, Curtis L.
AU - Gangula, Pandu
AU - Madhur, Meena S.
AU - Kalams, Spyros
AU - Mallal, Simon A.
AU - Harrison, David G.
AU - Beckman, Joshua A.
AU - Koethe, John R.
N1 - Funding Information:
This work was funded by NIH grants K23 100700 (J.K.), R01 DK112262 (J.R.K. and C.N.W.), HL131977 (J.B.), R56 DK108352 (J.R.K.), the Vanderbilt Clinical and Translational Science Award from NCRR/NIH grant UL1 RR024975, the Vanderbilt Infection Pathogenesis and Epidemiology Research Training Program (VIPER) grant T32 AI007474, CTSA award no. KL2 TR002245 from the National Center for Advancing Translational Sciences, and the Tennessee Center for AIDS Research grant P30 AI110527 (S.A.M.). The funding authorities had no role in study design; data collection, analysis, or interpretation; the decision to publish; or preparation of the manuscript.
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Objective:Chronic inflammation contributes to the high burden of cardiovascular disease (CVD) in persons with HIV (PWH). HIV has broad effects on innate and adaptive immune cells, including innate lymphoid cells (ILCs) and CD4+T-helper cells. At present, the relationship between CVD and plasma cytokines reflecting ILC/T-helper responses in PWH is not well defined. We investigated relationships between plasma cytokines and subclinical atherosclerosis.Design:A cross-sectional study.Methods:We recruited 70 PWH on a single antiretroviral regimen (efavirenz, teno- fovir, and emtricitabine) with at least 12 months of suppressed viremia and 30 HIVnegative controls. We quantified plasma cytokines and chemokines, including inter- feron-g, interleukin (IL)-4, IL-13, and IL-17A, markers of macrophage activation, and markers of endothelial activation using multiplex assays and ELISA. Cytokines were grouped using Ward's hierarchical clustering. Brachial artery flow-mediated dilation (FMD) and carotid plaque burden were determined using ultrasound. Multivariable linear regression and negative binomial regression analyses were used to assess the relationships of plasma biomarkers and endpoints adjusted for CVD risk factors.Results:We identified three distinct clusters in PWH, one containing Th1/Th2/ILC1/ ILC2 type cytokines, one with Th17/ILC3/macrophage-related cytokines, and a less specific third cluster. Lower FMD was associated with higher plasma IL-17A and macrophage inflammatory protein-1 a. In contrast, IL-4, a Th2/ILC2 type cytokine, was associated with carotid plaque. When HIV-negative controls were added to the models clustering was more diffuse, and these associations were attenuated or absent.Conclusion:Th17/ILC3 and Th2/ILC2-mediated immune mechanisms may have distinct roles in endothelial dysfunction and atherosclerotic plaque formation, respectively, in PWH.
AB - Objective:Chronic inflammation contributes to the high burden of cardiovascular disease (CVD) in persons with HIV (PWH). HIV has broad effects on innate and adaptive immune cells, including innate lymphoid cells (ILCs) and CD4+T-helper cells. At present, the relationship between CVD and plasma cytokines reflecting ILC/T-helper responses in PWH is not well defined. We investigated relationships between plasma cytokines and subclinical atherosclerosis.Design:A cross-sectional study.Methods:We recruited 70 PWH on a single antiretroviral regimen (efavirenz, teno- fovir, and emtricitabine) with at least 12 months of suppressed viremia and 30 HIVnegative controls. We quantified plasma cytokines and chemokines, including inter- feron-g, interleukin (IL)-4, IL-13, and IL-17A, markers of macrophage activation, and markers of endothelial activation using multiplex assays and ELISA. Cytokines were grouped using Ward's hierarchical clustering. Brachial artery flow-mediated dilation (FMD) and carotid plaque burden were determined using ultrasound. Multivariable linear regression and negative binomial regression analyses were used to assess the relationships of plasma biomarkers and endpoints adjusted for CVD risk factors.Results:We identified three distinct clusters in PWH, one containing Th1/Th2/ILC1/ ILC2 type cytokines, one with Th17/ILC3/macrophage-related cytokines, and a less specific third cluster. Lower FMD was associated with higher plasma IL-17A and macrophage inflammatory protein-1 a. In contrast, IL-4, a Th2/ILC2 type cytokine, was associated with carotid plaque. When HIV-negative controls were added to the models clustering was more diffuse, and these associations were attenuated or absent.Conclusion:Th17/ILC3 and Th2/ILC2-mediated immune mechanisms may have distinct roles in endothelial dysfunction and atherosclerotic plaque formation, respectively, in PWH.
KW - atherosclerosis
KW - cardiovascular disease
KW - endothelial dysfunction
KW - HIV
KW - interleukin-17
KW - interleukin-4
KW - T cells
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U2 - 10.1097/QAD.0000000000003196
DO - 10.1097/QAD.0000000000003196
M3 - Article
C2 - 35165215
AN - SCOPUS:85131271052
SN - 0269-9370
VL - 36
SP - 963
EP - 973
JO - AIDS
JF - AIDS
IS - 7
ER -