Correlation between CD4+CD28null T lymphocytes, regulatory T cells and plaque rupture: An Optical Coherence Tomography study in Acute Coronary Syndromes

Aureliano Ruggio, Daniela Pedicino, Davide Flego, Rocco Vergallo, Anna Severino, Claudia Lucci, Giampaolo Niccoli, Carlo Trani, Francesco Burzotta, Cristina Aurigemma, Antonio Maria Leone, Antonino Buffon, Alessia D'Aiello, Luigi Marzio Biasucci, Filippo Crea, Giovanna Liuzzo

Research output: Contribution to journalArticle

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 CD4+CD28null T-cells, lower regulatory T-cells (Treg) and increased CD4+CD28null/Treg ratio. We sought to investigate the correlation between CD4+CD28null T-cells, Treg, CD4+CD28null/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 CD4+CD28null and Treg (defined as CD4+CD25highCD127lowFoxp3+ T-cells) by flow-cytometry.

RESULTS: CD4+CD28null 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 CD4+CD28null/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 CD4+CD28null/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 CD4+CD28null 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.

Original languageEnglish
Pages (from-to)289-292
Number of pages4
JournalInternational Journal of Cardiology
Volume276
DOIs
Publication statusE-pub ahead of print - 2018

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Optical Coherence Tomography
Regulatory T-Lymphocytes
Acute Coronary Syndrome
Rupture
T-Lymphocytes
Stable Angina
Non-ST Elevated Myocardial Infarction
Adaptive Immunity
Atherosclerotic Plaques
Immune System
Blood Cells
Flow Cytometry
Phenotype

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Correlation between CD4+CD28null T lymphocytes, regulatory T cells and plaque rupture : An Optical Coherence Tomography study in Acute Coronary Syndromes. / Ruggio, Aureliano; Pedicino, Daniela; Flego, Davide; Vergallo, Rocco; Severino, Anna; Lucci, Claudia; Niccoli, Giampaolo; Trani, Carlo; Burzotta, Francesco; Aurigemma, Cristina; Leone, Antonio Maria; Buffon, Antonino; D'Aiello, Alessia; Biasucci, Luigi Marzio; Crea, Filippo; Liuzzo, Giovanna.

In: International Journal of Cardiology, Vol. 276, 2018, p. 289-292.

Research output: Contribution to journalArticle

@article{65d15c23716047f88d23ea1f7cc2b007,
title = "Correlation between CD4+CD28null T lymphocytes, regulatory T cells and plaque rupture: An Optical Coherence Tomography study in Acute Coronary Syndromes",
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 CD4+CD28null T-cells, lower regulatory T-cells (Treg) and increased CD4+CD28null/Treg ratio. We sought to investigate the correlation between CD4+CD28null T-cells, Treg, CD4+CD28null/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 CD4+CD28null and Treg (defined as CD4+CD25highCD127lowFoxp3+ T-cells) by flow-cytometry.RESULTS: CD4+CD28null 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 CD4+CD28null/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 CD4+CD28null/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 CD4+CD28null 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.",
author = "Aureliano Ruggio and Daniela Pedicino and Davide Flego and Rocco Vergallo and Anna Severino and Claudia Lucci and Giampaolo Niccoli and Carlo Trani and Francesco Burzotta and Cristina Aurigemma and Leone, {Antonio Maria} and Antonino Buffon and Alessia D'Aiello and Biasucci, {Luigi Marzio} and Filippo Crea and Giovanna Liuzzo",
note = "Copyright {\circledC} 2018 Elsevier B.V. All rights reserved.",
year = "2018",
doi = "10.1016/j.ijcard.2018.08.101",
language = "English",
volume = "276",
pages = "289--292",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Correlation between CD4+CD28null T lymphocytes, regulatory T cells and plaque rupture

T2 - An Optical Coherence Tomography study in Acute Coronary Syndromes

AU - Ruggio, Aureliano

AU - Pedicino, Daniela

AU - Flego, Davide

AU - Vergallo, Rocco

AU - Severino, Anna

AU - Lucci, Claudia

AU - Niccoli, Giampaolo

AU - Trani, Carlo

AU - Burzotta, Francesco

AU - Aurigemma, Cristina

AU - Leone, Antonio Maria

AU - Buffon, Antonino

AU - D'Aiello, Alessia

AU - Biasucci, Luigi Marzio

AU - Crea, Filippo

AU - Liuzzo, Giovanna

N1 - Copyright © 2018 Elsevier B.V. All rights reserved.

PY - 2018

Y1 - 2018

N2 - 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 CD4+CD28null T-cells, lower regulatory T-cells (Treg) and increased CD4+CD28null/Treg ratio. We sought to investigate the correlation between CD4+CD28null T-cells, Treg, CD4+CD28null/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 CD4+CD28null and Treg (defined as CD4+CD25highCD127lowFoxp3+ T-cells) by flow-cytometry.RESULTS: CD4+CD28null 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 CD4+CD28null/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 CD4+CD28null/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 CD4+CD28null 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.

AB - 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 CD4+CD28null T-cells, lower regulatory T-cells (Treg) and increased CD4+CD28null/Treg ratio. We sought to investigate the correlation between CD4+CD28null T-cells, Treg, CD4+CD28null/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 CD4+CD28null and Treg (defined as CD4+CD25highCD127lowFoxp3+ T-cells) by flow-cytometry.RESULTS: CD4+CD28null 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 CD4+CD28null/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 CD4+CD28null/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 CD4+CD28null 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.

U2 - 10.1016/j.ijcard.2018.08.101

DO - 10.1016/j.ijcard.2018.08.101

M3 - Article

C2 - 30217424

VL - 276

SP - 289

EP - 292

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -