Dominic C Chow, Jamie M Kagihara, Guangxiang Zhang, Scott A Souza, Howard N Hodis, Yanjie Li, Brooks I Mitchell, Beau K Nakamoto, Kalpana J Kallianpur, Sheila M Keating, Philip J Norris, Lindsay B Kohorn, Lishomwa C Ndhlovu, Cecilia M Shikuma
{"title":"非典型单核细胞可预测接受稳定抗逆转录病毒治疗的艾滋病病毒感染者颈动脉分叉处内膜中层厚度的进展。","authors":"Dominic C Chow, Jamie M Kagihara, Guangxiang Zhang, Scott A Souza, Howard N Hodis, Yanjie Li, Brooks I Mitchell, Beau K Nakamoto, Kalpana J Kallianpur, Sheila M Keating, Philip J Norris, Lindsay B Kohorn, Lishomwa C Ndhlovu, Cecilia M Shikuma","doi":"10.1080/15284336.2016.1162386","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892178/pdf/nihms788088.pdf","citationCount":"0","resultStr":"{\"title\":\"Non-classical monocytes predict progression of carotid artery bifurcation intima-media thickness in HIV-infected individuals on stable antiretroviral therapy.\",\"authors\":\"Dominic C Chow, Jamie M Kagihara, Guangxiang Zhang, Scott A Souza, Howard N Hodis, Yanjie Li, Brooks I Mitchell, Beau K Nakamoto, Kalpana J Kallianpur, Sheila M Keating, Philip J Norris, Lindsay B Kohorn, Lishomwa C Ndhlovu, Cecilia M Shikuma\",\"doi\":\"10.1080/15284336.2016.1162386\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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. 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引用次数: 0
摘要
背景:在抗逆转录病毒抑制的艾滋病病毒感染者中,炎症可能会导致心血管疾病(CVD)。我们评估了单核细胞、CD8 T细胞活化和血浆生物标志物与颈动脉内膜中层厚度(CIMT)变化的关系:方法:对年龄≥40 岁、接受稳定抗逆转录病毒疗法(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核细胞进行免疫分型,以量化经典(CD14(++)CD16(-))、中间(CD14(++)CD16(+))、非经典(CD14(低/+)CD16(++))和过渡(CD14(+)CD16(-))单核细胞亚群和活化(CD38(+)HLA-DR(+))的CD8(+)CD8(+) T 细胞。血浆生物标志物通过多重 Luminex 检测法进行评估。对右颈动脉进行高分辨率 B 型超声检查。右侧颈总动脉(CIMTCCA)和右侧分叉处(CIMTBIF)两年内的CIMT变化是结果变量:我们对 50 名受试者进行了研究:84%为男性,中位年龄49(Q1,Q3;46,56)岁,中位CD4细胞数461(317,578)个/mm(3),84%的人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。在多变量线性回归中,只有非典型单核细胞和 MCP-1 可以预测 CIMTBIF 的变化,而与弗雷明汉风险评分和基线 CIMTBIF 无关。CD8 T 细胞活化与 CIMTBIF 变化之间没有相关性。单核细胞亚群、CD8 T细胞活化和生物标志物浓度与CIMTCCA的变化无关:我们的研究结果强调了非典型单核细胞和 MCP-1 在接受稳定抗逆转录病毒疗法的 HIV 感染者的 CIMTBIF 进展中的作用,而与传统的心血管代谢风险因素无关。
Non-classical monocytes predict progression of carotid artery bifurcation intima-media thickness in HIV-infected individuals on stable antiretroviral therapy.
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.
期刊介绍:
HIV Clinical Trials is devoted exclusively to presenting information on the latest developments in HIV/AIDS clinical research. This journal enables readers to obtain the most up-to-date, innovative research from around the world.