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CD4CD28T 淋巴细胞、调节性 T 细胞与斑块破裂的相关性:急性冠状动脉综合征的光学相干断层扫描研究。

Correlation between CD4CD28 T lymphocytes, regulatory T cells and plaque rupture: An Optical Coherence Tomography study in Acute Coronary Syndromes.

机构信息

Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Rome, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Rome, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

出版信息

Int J Cardiol. 2019 Feb 1;276:289-292. doi: 10.1016/j.ijcard.2018.08.101. Epub 2018 Sep 7.

DOI:10.1016/j.ijcard.2018.08.101
PMID:30217424
Abstract

BACKGROUND

A sizeable proportion of patients with Acute Coronary Syndromes (ACS) shows a unique adaptive immune system profile, associated to a worse outcome, characterized by higher CD4CD28 T-cells, lower regulatory T-cells (Treg) and increased CD4CD28/Treg ratio. We sought to investigate the correlation between CD4CD28 T-cells, Treg, CD4CD28/Treg ratio and plaque phenotype as assessed by Optical Coherence Tomography (OCT).

METHODS

Peripheral blood mononuclear cells (PBMC) were collected from 30 Non-ST Elevation Myocardial Infarction (NSTEMI) patients, sub-grouped according to OCT analysis of culprit lesions into two cohorts: Ruptured Fibrous Cap (NSTEMI-RFC, n = 12) and Intact Fibrous Cap (NSTEMI-IFC, n = 18). Stable Angina patients (SA, n = 18) were used as controls. We examined the frequency of CD4CD28 and Treg (defined as CD4CD25CD127Foxp3 T-cells) by flow-cytometry.

RESULTS

CD4CD28 frequency (median, range) was significantly higher in NSTEMI-RFC patients (17.3%, 12.5-33.8) as compared with NSTEMI-IFC (3.8%, 0.3-14.1) and SA (3%, 0.6-17.7) (P < 0.001 for all comparisons). We also found a higher CD4CD28/Treg ratio in NSTEMI-RFC patients (6.6%, 3.7-13.9) than in NSTEMI-IFC (1.6%, 0.3-5.2) and SA (1.2%, 0.3-8.7) (P < 0.001 for all comparisons). Finally, there was an inverse correlation between CD4CD28/Treg ratio and cap-thickness (R = -0.44; P = 0.002).

CONCLUSION

Patients with NSTEMI presenting with RFC as culprit lesion at OCT evaluation have a specific perturbation of adaptive immunity, mostly involving CD4CD28 T- cells and Tregs, as compared with patients with IFC and SA. This specific imbalance of T-cells might play a key role in fibrous cap thinning, predisposing atherosclerotic plaque to rupture.

摘要

背景

相当一部分急性冠状动脉综合征(ACS)患者表现出独特的适应性免疫系统特征,与更差的预后相关,其特征为 CD4CD28 T 细胞更高、调节性 T 细胞(Treg)更低以及 CD4CD28/Treg 比值增加。我们旨在通过光相干断层扫描(OCT)评估斑块表型,来研究 CD4CD28 T 细胞、Treg、CD4CD28/Treg 比值与斑块表型之间的相关性。

方法

从 30 例非 ST 段抬高型心肌梗死(NSTEMI)患者中采集外周血单个核细胞(PBMC),根据罪犯病变的 OCT 分析将患者分为两组:破裂纤维帽(NSTEMI-RFC,n=12)和完整纤维帽(NSTEMI-IFC,n=18)。稳定型心绞痛(SA)患者(n=18)作为对照组。我们通过流式细胞术检测 CD4CD28 和 Treg(定义为 CD4CD25CD127Foxp3 T 细胞)的频率。

结果

与 NSTEMI-IFC(3.8%,0.3-14.1)和 SA(3%,0.6-17.7)相比,NSTEMI-RFC 患者的 CD4CD28 频率(中位数,范围)显著更高(17.3%,12.5-33.8)(所有比较 P<0.001)。我们还发现 NSTEMI-RFC 患者的 CD4CD28/Treg 比值(6.6%,3.7-13.9)高于 NSTEMI-IFC(1.6%,0.3-5.2)和 SA(1.2%,0.3-8.7)(所有比较 P<0.001)。最后,CD4CD28/Treg 比值与帽厚度呈负相关(R=-0.44;P=0.002)。

结论

与 IFC 和 SA 患者相比,OCT 评估为破裂纤维帽为罪犯病变的 NSTEMI 患者的适应性免疫存在特定的紊乱,主要涉及 CD4CD28 T 细胞和 Tregs。这种 T 细胞的特定失衡可能在纤维帽变薄中起关键作用,使动脉粥样硬化斑块易于破裂。

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