Differences in immune responses between CMV-seronegative and -seropositive patients with myocardial ischemia and reperfusion.

Evgeniya V Shmeleva,Karim Bennaceur,Ioakim Spyridopoulos,Mohaned Egred,Stephen E Boag,Richard Edwards,Santosh Murali,Rajiv Das,Stephen Todryk,Ian Purcell

doi:10.1002/iid3.49

Evgeniya V Shmeleva, Karim Bennaceur + Show 8 more

Open Access

https://doi.org/10.1002/iid3.49

Copy DOI

Abstract

CMV infection is responsible for acceleration of immune senescence and linked to systemic pathologies, including cardiovascular diseases. In this study, we investigated differences in the immune response between CMV-seropositive and seronegative patients undergoing primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (MI). Peripheral blood samples were taken at six different time points: pre-, 15, 30, 90 min, 24 h after PPCI and at 3 months after MI. Absolute counts of lymphocyte subpopulations, immune response to specific and nonspecific stimulation, serum cytokines and levels of CMV-IgG, cardiolipin-IgG, and anti-endothelial cell antibodies were assessed. CMV-seropositive patients with MI showed a twofold higher IFN-γ production to PHA-stimulation, up to 2.5-fold higher levels of IP-10 in serum and up to 30% lower serum levels of IL-16 compared to CMV-seronegative individuals. CMV-seropositive patients could be divided into two subgroups with high (IL-10Hi) and low (IL-10Lo) IL-10 serum levels during the acute stage of MI. The IL-10Hi CMV-seropositive subgroup showed an increased exit of late-differentiated T lymphocytes, NK and NKT-like cells from the circulation, which may potentially enhance cytotoxic damage in the ischemic myocardium. Finally, we did not observe an acceleration of autoimmunity by MI in CMV-seropositive individuals. The immune response during acute MI showed characteristic differences between CMV seronegative and seropositive patients, with a stronger pro-inflammatory response in seropositive patients. The effects of IP-10, IL-16, and IL-10 on characteristics of acute immune responses and formation of different immune profiles in CMV-seropositive individuals require further investigation.

Highlights

Every year approximately 25,000 patients in the UK undergo reperfusion therapy for acute myocardial infarction, in most cases by primary percutaneous coronary intervention (PPCI), which involves opening of the blocked coronary artery followed by placing a stent [1]
We have shown previously that reopening of an occluded coronary artery with PPCI during acute myocardial infarction (MI) leads to an acute depletion of T cells from peripheral blood [6]
We demonstrate that CMVseropositive and seronegative patients show different dynamics in nonspecific IFN-g production, as well as IP10 and IL-16 expression in the serum during acute MI

Summary

Introduction

Every year approximately 25,000 patients in the UK undergo reperfusion therapy for acute myocardial infarction, in most cases by primary percutaneous coronary intervention (PPCI), which involves opening of the blocked coronary artery followed by placing a stent [1]. Major recent improvements in PPCI and associated therapies have lead to a reduction in acute mortality. There are two major reasons for this, the first of which relates to the size of the infarct, culminating in left ventricular dysfunction and eventually leading to heart failure. The other is the accelerated progression of atherosclerosis following myocardial infarction (MI), which could be explained by the pro-inflammatory state of such patients. In particular lymphocytes, regulate inflammation, their role in myocardial infarction has not been investigated in detail

Objectives

Methods

Results

Conclusion