Decreased human leukocyte antigen-D-related expression on CD14⁺ monocytes in patients with out-of-hospital cardiac arrest provided target temperature management therapy: a prospective observational study

Abstract

Background: Post-cardiac arrest syndrome involves systemic inflammation, which causes subsequent neurological impairments. We investigated the influence of targeted temperature management (TTM) therapy in patients with out-of-hospital cardiac arrest (OHCA) after return of spontaneous circulation (ROSC) by observing the changes in circulating CD14⁺ monocytes and the expression of human leukocyte antigen D-related (HLA-DR) and programmed cell death ligand 1 (PD-L1) in CD14⁺ monocytes.

Methods: Adult patients admitted to the emergency department of Beijing Chao-Yang Hospital after OHCA between January 2017 and March 2018 were included in this study. Thirty control subjects, 10 patients with OHCA, and 37 patients with OHCA who received 72 hours of TTM therapy were enrolled. Peripheral blood samples of patients in the OHCA and TTM groups were collected on Days 1 and 3 (D1 and D3) after ROSC and evaluated for HLA-DR and PD-L1 expression on CD14⁺ monocytes using flow cytometry.

Results: Compared with control subjects, the percentage of circulating CD14⁺ monocytes, HLA-DR⁺/CD14⁺ monocyte ratios, and mean fluorescence intensity were significantly decreased in patients with OHCA. After ROSC, HLA-DR expression in CD14 ⁺ monocytes in the TTM group was lower than that in patients with OHCA. However, there were no significant differences in the percentage of PD-L1⁺/CD14⁺ monocytes or the mean fluorescence intensity between patients with OHCA and healthy volunteers.

Conclusion: After ROSC, circulating CD14⁺ monocytes and HLA-DR⁺/CD14⁺ monocyte ratios decreased significantly in patients with OHCA. Human leukocyte antigen D-related expression in CD14⁺ monocytes was lower in patients treated with TTM.

Keywords

Human leukocyte antigen D-related / Monocytes / Out-of-hospital cardiac arrest / Target temperature management

Conflict of interest

Chunsheng Li is an Associate Editor of Emergency and Critical Care Medicine. The article was subject to the journal’s standard procedures, with peer reviews handled independently of this Associate Editor and their research groups. The authors declare no conflict of interest.

Author contributions

Shao H contributed to the study design, method development, data interpretation, and manuscript writing. Yuan W, Tang Z, Qi Z, An L, and Zhang Q contributed to the experimental design of the studies and conducted experiments. Li C conceived the study design, coordinated the experiments, helped draft the manuscript, and finalized the manuscript. All the authors have read and approved the final version of the manuscript.

Funding

This work was supported by the National Natural Science Founda-tion of China (Grant No. 81372025).

Ethical approval of studies and informed consent

The study followed the principles of the Declaration of Helsinki as revised in 2013. This study was approved by the Medical Ethics Committee of the Beijing Chao-Yang Hospital (No. 2013-KE-1). Approval date: January 10, 2013. Written informed consent was obtained from all the patients (when possible) and volunteers. Consent for patients who were unable to respond was obtained from their first-degree relatives. This manuscript obtains the consent of the patient for the use of their data and the publication of the data that appear in the article.

Acknowledgments

None.

References

[1] Wissenberg M, Lippert FK, Folke F, et al. Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest. JAMA. 2013; 310(13):1377-1384. doi:10.1001/jama.2013.278483

[2] Stub D, Bernard S, Duffy SJ, Kaye DM. Post cardiac arrest syndrome: a review of therapeutic strategies. Circulation. 2011; 123(13):1428-1435. doi:10.1161/CIRCULATIONAHA.110.988725

[3] Peigne V, Azoulay E, Coquet I, et al. The prognostic value of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency in septic shock patients involves interleukin-6 and is not dependent on disseminated intravascular coagulation. Crit Care. 2013; 17(6):R273. doi:10.1186/cc13115

[4] Samaniego EA, Persoon S, Wijman CA. Prognosis after cardiac arrest and hypothermia: a new paradigm. Curr Neurol Neurosci Rep. 2011; 11(1):111-119. doi:10.1007/s11910-010-0148-9

[5] Taccone FS, Picetti E, Vincent JL. High quality targeted temperature management (TTM) after cardiac arrest. Crit Care. 2020; 24(1):6. doi:10.1186/s13054-019-2721-1

[6] Hosseini M, Wilson RH, Crouzet C, Amirhekmat A, Wei KS, Akbari Y. Resuscitating the globally ischemic brain: TTM and beyond. Neurotherapeutics. 2020; 17(2):539-562. doi:10.1007/s13311-020-00856-z

[7] Mody P, Kulkarni N, Khera R, Link MS. Targeted temperature management for cardiac arrest. Prog Cardiovasc Dis. 2019; 62(3):272-278. doi:10.1016/j.pcad.2019.05.007

[8] Granfeldt A, Holmberg MJ, Nolan JP, Soar J, Andersen LW; International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force. Targeted temperature management in adult cardiac arrest: systematic review and meta-analysis. Resuscitation. 2021; 167:160-172. doi:10.1016/j.resuscitation.2021.08.040

[9] Kimura A, Sakurada S, Ohkuni H, Todome Y, Kurata K. Moderate hypothermia delays proinflammatory cytokine production of human peripheral blood mononuclear cells. Crit Care Med. 2002; 30(7):1499-1502. doi:10.1097/00003246-200207000-00017

[10] Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. 2009; 37(7 suppl):S186-S202. doi:10.1097/CCM.0b013e3181aa5241

[11] de Roquetaillade C, Dupuis C, Faivre V, Lukaszewicz AC, Brumpt C, Payen D. Monitoring of circulating monocyte HLA-DR expression in a large cohort of intensive care patients: relation with secondary infections. Ann Intensive Care. 2022; 12(1):39. doi:10.1186/s13613-022-01010-y

[12] Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol. 2007; 19(7):813-824. doi:10.1093/intimm/dxm057

[13] Nurieva RI, Liu X, Dong C. Yin-yang of costimulation: crucial controls of immune tolerance and function. Immunol Rev. 2009; 229(1):88-100. doi:10.1111/j.1600-065X.2009.00769.x

[14] Lee JT, Mikkelsen ME. Risk stratification tools in sepsis: from Acute Physiology and Chronic Health Evaluation to quick Sequential Organ Failure Assessment. Crit Care Med. 2019; 47(8):1159-1161. doi:10.1097/CCM.0000000000003859

[15] Czerwińska-Jelonkiewicz K, Grand J, Tavazzi G, et al. Acute respiratory failure and inflammatory response after out-of-hospital cardiac arrest: results of the post-cardiac arrest syndrome (PCAS) pilot study. Eur Heart J Acute Cardiovasc Care. 2020; 9(4_suppl):S110-S121. doi:10.1177/2048872619895126

[16] Grimaldi D, Sauneuf B, Guivarch E, et al. High level of endotoxemia following out-of-hospital cardiac arrest is associated with severity and duration of postcardiac arrest shock. Crit Care Med. 2015; 43(12):2597-2604. doi:10.1097/CCM.0000000000001303

[17] Mongardon N, Perbet S, Lemiale V, et al. Infectious complications in out-of-hospital cardiac arrest patients in the therapeutic hypothermia era. Crit Care Med. 2011; 39(6):1359-1364. doi:10.1097/CCM.0b013e3182120b56

[18] Beurskens CJ, Horn J, de Boer AM, et al. Cardiac arrest patients have an impaired immune response, which is not influenced by induced hypothermia. Crit Care. 2014; 18(4):R162. doi:10.1186/cc14002

[19] Su C-P, Wu J-H, Yang M-C, et al. Demographics and clinical features of postresuscitation comorbidities in long-term survivors of out-of-hospital cardiac arrest: a national follow-up study. Biomed Res Int. 2017; 2017:9259182. doi:10.1155/2017/9259182

[20] Qi Z, An L, Liu B, et al. Patients with out-of-hospital cardiac arrest show decreased human leucocyte antigen-DR expression on monocytes and B and T lymphocytes after return of spontaneous circulation. Scand J Immunol. 2018; 88(4):e12707. doi:10.1111/sji.12707

[21] Leventogiannis K, Kyriazopoulou E, Antonakos N, et al. Toward personalized immunotherapy in sepsis: the PROVIDE randomized clinical trial. Cell Rep Med. 2022; 3(11):100817. doi:10.1016/j.xcrm.2022.100817

[22] Polderman KH, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med. 2009; 37(3):1101-1120. doi:10.1097/CCM.0b013e3181962ad5

[23] Dietrich WD, Chatzipanteli K, Vitarbo E, Wada K, Kinoshita K. The role of inflammatory processes in the pathophysiology and treatment of brain and spinal cord trauma. Acta Neurochir Suppl. 2004; 89:69-74. doi:10.1007/978-3-7091-0603-7_9

[24] Suehiro E, Fujisawa H, Akimura T, et al. Increased matrix metalloproteinase-9 in blood in association with activation of interleukin-6 after traumatic brain injury: influence of hypothermic therapy. J Neurotrauma. 2004; 21(12):1706-1711. doi:10.1089/neu.2004.21.1706

[25] Polderman KH. Hypothermia, immune suppression and SDD: can we have our cake and eat it?. Crit Care. 2011; 15(2):144. doi:10.1186/cc10080

[26] Polderman KH. Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet. 2008; 371(9628):1955-1969. doi:10.1016/S0140-6736(08)60837-5