非经典单核细胞可预测接受稳定抗逆转录病毒治疗的HIV感染者颈动脉分叉处内膜中层厚度的进展。
Non-classical monocytes predict progression of carotid artery bifurcation intima-media thickness in HIV-infected individuals on stable antiretroviral therapy.
作者信息
Chow Dominic C, Kagihara Jamie M, Zhang Guangxiang, Souza Scott A, Hodis Howard N, Li Yanjie, Mitchell Brooks I, Nakamoto Beau K, Kallianpur Kalpana J, Keating Sheila M, Norris Philip J, Kohorn Lindsay B, Ndhlovu Lishomwa C, Shikuma Cecilia M
机构信息
a Hawaii Center for AIDS, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA.
b The Queen's Medical Center , Honolulu , HI , USA.
出版信息
HIV Clin Trials. 2016 May;17(3):114-22. doi: 10.1080/15284336.2016.1162386. Epub 2016 Apr 4.
BACKGROUND
Inflammation may contribute to cardiovascular disease (CVD) among antiretrovirally suppressed HIV-infected individuals. We assessed relationships of monocyte, CD8 T-cell activation and plasma biomarkers to changes in carotid artery intima-media thickness (CIMT).
METHODS
Longitudinal study of HIV-infected subjects ≥40 years and on stable antiretroviral therapy (ART) ≥3 months. Peripheral blood mononuclear cells were immunophenotyped by multiparameteric flow cytometry to quantify classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), non-classical (CD14(low/+)CD16(++)) and transitional (CD14(+)CD16(-)) monocyte subsets and activated (CD38(+)HLA-DR(+)) CD8(+) T-cells at baseline. Plasma biomarkers were assessed by multiplex Luminex assay. High-resolution B-mode ultrasounds of right carotid arteries were obtained. Changes in CIMT over two years at the right common carotid artery (CIMTCCA) and right bifurcation (CIMTBIF) were outcome variables.
RESULTS
We studied 50 subjects: 84% male, median age 49 (Q1, Q3; 46, 56) years, median CD4 count 461 (317, 578) cells/mm(3), and with HIV RNA ≤ 50 copies/mL in 84%. Change in CIMTBIF correlated with log values of baseline absolute count of non-classical monocytes (r = 0.37, p = 0.020), and with MCP-1 (r = 0.42, p = 0.0024) and TNF-α (r = 0.30, p = 0.036) levels. In multivariable linear regression, only non-classical monocytes and MCP-1 predicted the change in CIMTBIF, independent of Framingham Risk Score and baseline CIMTBIF. No correlation was noted between CD8 T-cell activation and CIMTBIF change. Monocyte subsets, CD8 T-cell activation, and biomarker concentrations were not correlated with changes in CIMTCCA.
CONCLUSIONS
Our findings highlight the role of non-classical monocytes and MCP-1 in the progression of CIMTBIF in HIV-infected individuals on stable ART independent of traditional cardio-metabolic risk factors.
背景
在接受抗逆转录病毒治疗且病情得到抑制的HIV感染者中，炎症可能促使心血管疾病（CVD）的发生。我们评估了单核细胞、CD8 T细胞活化及血浆生物标志物与颈动脉内膜中层厚度（CIMT）变化之间的关系。
方法
对年龄≥40岁且接受稳定抗逆转录病毒治疗（ART）≥3个月的HIV感染者进行纵向研究。通过多参数流式细胞术对外周血单个核细胞进行免疫表型分析，以定量分析基线时经典型（CD14(++)CD16(-)）、中间型（CD14(++)CD16(+)）、非经典型（CD14(low/+)CD16(++)）和过渡型（CD14(+)CD16(-)）单核细胞亚群以及活化型（CD38(+)HLA-DR(+)）CD8(+) T细胞。通过多重Luminex检测法评估血浆生物标志物。获取右侧颈动脉的高分辨率B型超声图像。右侧颈总动脉（CIMTCCA）和右侧分叉处（CIMTBIF）两年内CIMT的变化为观察指标。
结果
我们研究了50名受试者：男性占84%，年龄中位数为49（四分位间距Q1, Q3；46, 56）岁，CD4细胞计数中位数为461（317, 578）个/立方毫米，84%的受试者HIV RNA≤50拷贝/毫升。CIMTBIF的变化与非经典单核细胞基线绝对计数的对数值相关（r = 0.37，p = 0.020），与MCP-1（r = 0.42，p = 0.0024）和TNF-α（r = 0.30，p = 0.036）水平相关。在多变量线性回归分析中，仅非经典单核细胞和MCP-1可预测CIMTBIF的变化，不受弗雷明汉风险评分和基线CIMTBIF的影响。未发现CD8 T细胞活化与CIMTBIF变化之间存在相关性。单核细胞亚群、CD8 T细胞活化及生物标志物浓度与CIMTCCA的变化无关。
结论
我们的研究结果突出了非经典单核细胞和MCP-1在接受稳定ART治疗的HIV感染者CIMTBIF进展中的作用，且该作用独立于传统的心脏代谢风险因素。
Zotero 插件