Elevated Plasma Soluble PD-L1 Levels in Out-of-Hospital Cardiac Arrest Patients.

Miho Sumiyoshi,Ryo Esumi,Kaoru Ikejiri,Yuki Nakamori,Motomu Shimaoka,Asami Ito-Masui,Hiroshi Imai,Eun Jeong Park,Eiji Kawamoto,Toru Shinkai,Yuichi Akama,Arong Gaowa

doi:10.3390/jcm10184188

Miho Sumiyoshi, Ryo Esumi + Show 10 more

Open Access

https://doi.org/10.3390/jcm10184188

Copy DOI

Abstract

Background: A deregulated immune system has been implicated in the pathogenesis of post-cardiac arrest syndrome (PCAS). A soluble form of programmed cell death-1 (PD-1) ligand (sPD-L1) has been found at increased levels in cancer and sustained inflammation, thereby deregulating immune functions. Here, we aim to study the possible involvement of sPD-L1 in PCAS. Methods: Thirty out-of-hospital cardiac arrest (OHCA) patients consecutively admitted to the ER of Mie University Hospital were prospectively enrolled. Plasma concentrations of sPD-L1 were measured by an enzyme-linked immunosorbent assay in blood samples of all 30 OHCA patients obtained during cardiopulmonary resuscitation (CPR). In 13 patients who achieved return-of-spontaneous-circulation (ROSC), sPD-L1 levels were also measured daily in the ICU. Results: The plasma concentrations of sPD-L1 in OHCA were significantly increased; in fact, to levels as high as those observed in sepsis. sPD-L1 levels during CPR correlated with reduced peripheral lymphocyte counts and increased C-reactive protein levels. Of 13 ROSC patients, 7 cases survived in the ICU for more than 4 days. A longitudinal analysis of sPD-L1 levels in the 7 ROSC cases revealed that sPD-L1 levels occurred in parallel with organ failure. Conclusions: This study suggests that ischemia- reperfusion during CPR may aberrantly activate immune and endothelial cells to release sPD-L1 into circulation, which may play a role in the pathogenesis of immune exhaustion and organ failures associated with PCAS.

Highlights

Post-cardiac arrest syndrome (PCAS), which occurs in resuscitated patients undergoing cardiac arrest, is characterized by four key pathological manifestations including post-cardiac arrest brain injury, post-cardiac arrest myocardial dysfunction, systemic ischemia-reperfusion, and persistent precipitating pathophysiology [1,2,3]
cardiopulmonary resuscitation (CPR), we found that they correlated with increased blood urea nitrogen (BUN) and creatinine (Cre) and decreased estimated glomerular filtration rate
The increased sPD-L1 levels are thought to result from ischemia-reperfusion, because, even before ROSC, circulatory support by CPR with chest compressions partially restored tissue perfusion, thereby activating the mechanisms that lead to ischemia-reperfusion injury [21]

Summary

Introduction

Post-cardiac arrest syndrome (PCAS), which occurs in resuscitated patients undergoing cardiac arrest, is characterized by four key pathological manifestations including post-cardiac arrest brain injury, post-cardiac arrest myocardial dysfunction, systemic ischemia-reperfusion, and persistent precipitating pathophysiology [1,2,3]. An ischemia-reperfusion injury that systemically occurs in PCAS induces a deregulated immune response and sustained inflammation, resembling the pathophysiology of sepsis [5]. Immune-suppression represents an important pathology involved in sepsis, and in PCAS, thereby increasing the risk of such infections as pneumonia during postcardiac arrest care [6]. The plasma samples of PCAS patients have been shown to contain immunosuppressive activities, thereby inhibiting cytokine production of circulating leukocytes [5]. Plasma concentrations of sPD-L1 were measured by an enzyme-linked immunosorbent assay in blood samples of all 30 OHCA patients obtained during cardiopulmonary resuscitation (CPR). Results: The plasma concentrations of sPD-L1 in OHCA were significantly increased; to levels as high as those observed in sepsis

Objectives

Results

Discussion

Conclusion