固有免疫和适应性免疫细胞亚群作为两个基于人群队列的冠心病危险因素。
Innate and adaptive immune cell subsets as risk factors for coronary heart disease in two population-based cohorts.
机构信息
Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, USA.
Department of Medicine, University of Washington, Seattle, WA, USA; Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
出版信息
Atherosclerosis. 2020 May;300:47-53. doi: 10.1016/j.atherosclerosis.2020.03.011. Epub 2020 Mar 16.
BACKGROUND AND AIMS
Cell-mediated immunity is implicated in atherosclerosis. We evaluated whether innate and adaptive immune cell subsets in peripheral blood are risk factors for coronary heart disease.
METHODS
A nested case-cohort study (n = 2155) was performed within the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS). Cases of incident myocardial infarction (MI) and incident angina (n = 880 total cases) were compared with a cohort random sample (n = 1275). Immune cell phenotypes (n = 34, including CD14 monocytes, natural killer cells, γδ T cells, CD4, CD8 and CD19 lymphocyte subsets) were measured from cryopreserved cells by flow cytometry. Cox proportional hazards models with adjustment for cardiovascular disease risk factors were used to evaluate associations of cell phenotypes with incident MI and a composite phenotype of incident MI or incident angina (MI-angina) over a median 9.3 years of follow-up. Th1, Th2, Th17, T regulatory (CD4CD25CD127), naive (CD4CD45RA), memory (CD4CD45RO), and CD4CD28 cells were specified as primary hypotheses. In secondary analyses, 27 additional cell phenotypes were investigated.
RESULTS
After correction for multiple testing, there were no statistically significant associations of CD4 naive, memory, CD28, or T helper cell subsets with MI or MI-angina in MESA, CHS, or combined-cohort meta analyses. Null associations were also observed for monocyte subsets, natural killer cells, γδ T cells, CD19 B cell and differentiated CD4 and CD8 cell subsets.
CONCLUSIONS
The proportions of peripheral blood monocyte and lymphocyte subsets are not strongly related to the future occurrence of MI or angina in adults free of autoimmune disease.
背景与目的
细胞介导的免疫反应与动脉粥样硬化有关。我们评估了外周血固有免疫和适应性免疫细胞亚群是否是冠心病的危险因素。
方法
采用多民族动脉粥样硬化研究（MESA）和心血管健康研究（CHS）的巢式病例对照研究（n=2155）。将心肌梗死（MI）和心绞痛（angina）的新发病例（n=880 例总病例）与队列随机样本（n=1275 例）进行比较。通过流式细胞术从冷冻细胞中测量免疫细胞表型（n=34，包括 CD14 单核细胞、自然杀伤细胞、γδ T 细胞、CD4、CD8 和 CD19 淋巴细胞亚群）。使用 Cox 比例风险模型，在调整心血管疾病危险因素后，评估细胞表型与 MI 新发病例以及 MI 或心绞痛新发病例的复合表型（MI-angina）之间的关联，中位随访时间为 9.3 年。Th1、Th2、Th17、T 调节（CD4CD25CD127）、幼稚（CD4CD45RA）、记忆（CD4CD45RO）和 CD4CD28 细胞被指定为主要假设。在二次分析中，研究了 27 个额外的细胞表型。
结果
经过多次检验校正后，在 MESA、CHS 或联合队列荟萃分析中，CD4 幼稚、记忆、CD28 或辅助性 T 细胞亚群与 MI 或 MI-angina 之间没有统计学显著关联。单核细胞亚群、自然杀伤细胞、γδ T 细胞、CD19 B 细胞和分化的 CD4 和 CD8 细胞亚群也观察到了类似的结果。
结论
在无自身免疫性疾病的成年人中，外周血单核细胞和淋巴细胞亚群的比例与未来发生 MI 或心绞痛的相关性不强。
Zotero 插件