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 + CD28 null T-cells, lower regulatory T-cells (Treg) and increased CD4 + CD28 null /Treg ratio. We sought to investigate the correlation between CD4 + CD28 null T-cells, Treg, CD4 + CD28 null /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 + CD28 null and Treg (defined as CD4 + CD25 high CD127 low Foxp3 + T-cells) by flow-cytometry. Results: CD4 + CD28 null 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 + CD28 null /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 + CD28 null /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 + CD28 null 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.

Ruggio, A., Pedicino, D., Flego, D., Vergallo, R., Severino, A., Lucci, C., Niccoli, G., Trani, C., Burzotta, F., Aurigemma, C., Leone, A. M., Buffon, A. M. T., D'Aiello, A., Biasucci, L. M., Crea, F., Liuzzo, G., Correlation between CD4 + CD28 null T lymphocytes, regulatory T cells and plaque rupture: An Optical Coherence Tomography study in Acute Coronary Syndromes, <<INTERNATIONAL JOURNAL OF CARDIOLOGY>>, 2019; 276 (feb): 289-292. [doi:10.1016/j.ijcard.2018.08.101] [http://hdl.handle.net/10807/131830]

Correlation between CD4 + CD28 null 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 Maria Tommaso;D'Aiello, Alessia;Biasucci, Luigi Marzio;Crea, Filippo;Liuzzo, Giovanna
2019

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 + CD28 null T-cells, lower regulatory T-cells (Treg) and increased CD4 + CD28 null /Treg ratio. We sought to investigate the correlation between CD4 + CD28 null T-cells, Treg, CD4 + CD28 null /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 + CD28 null and Treg (defined as CD4 + CD25 high CD127 low Foxp3 + T-cells) by flow-cytometry. Results: CD4 + CD28 null 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 + CD28 null /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 + CD28 null /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 + CD28 null 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.
2019
Inglese
Ruggio, A., Pedicino, D., Flego, D., Vergallo, R., Severino, A., Lucci, C., Niccoli, G., Trani, C., Burzotta, F., Aurigemma, C., Leone, A. M., Buffon, A. M. T., D'Aiello, A., Biasucci, L. M., Crea, F., Liuzzo, G., Correlation between CD4 + CD28 null T lymphocytes, regulatory T cells and plaque rupture: An Optical Coherence Tomography study in Acute Coronary Syndromes, <<INTERNATIONAL JOURNAL OF CARDIOLOGY>>, 2019; 276 (feb): 289-292. [doi:10.1016/j.ijcard.2018.08.101] [http://hdl.handle.net/10807/131830]
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