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

• Main Authors: Miho Sumiyoshi, Eiji Kawamoto, Yuki Nakamori, Ryo Esumi, Kaoru Ikejiri, Toru Shinkai, Yuichi Akama, Asami Ito-Masui, Hiroshi Imai, Arong Gaowa, Eun Jeong Park, Motomu Shimaoka
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Journal of Clinical Medicine
• Subjects: post-cardiac arrest syndrome; immunosuppression; inflammation; PD-1; PD-L1; lymphocytes
• Online Access: https://www.mdpi.com/2077-0383/10/18/4188

<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.