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Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study

Wilson, JK; Zhao, Y; Singer, M; Spencer, J; Shankar-Hari, M; (2018) Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study. Critical Care , 22 , Article 95. 10.1186/s13054-018-2020-2. Green open access

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Abstract

Background Sepsis remains a major cause of mortality in critical care, for which specific treatments are lacking. The dysregulated response to infection seen in sepsis includes features of lymphocyte dysfunction and exhaustion, suggesting that immune-stimulatory therapy may improve outcomes in certain patient groups. Monoclonal antibodies targeting checkpoint molecules, such as programmed-death 1 protein (PD-1) and its ligand PD-L1, have shown success in stimulating the immune response in patients with cancer, and are being considered for future sepsis trials. The aims of this pilot study were to compare lymphocyte subset expression of PD-1 and its ligands between patients with sepsis and controls; to characterize serum levels of PD-1 and PD-L1 in patients with sepsis and controls, and determine if serum concentrations correlated with cell surface expression. Methods Expression levels of PD-1, PD-L1 and PD-L2 on four lymphocyte subsets (CD27 + CD19+ B cells, CD27-CD19+ B cells, CD27 + CD4+ T cells and CD27-CD4+ T cells) were compared between 22 patients with sepsis (including 11 survivors and 11 non-survivors) and 11 healthy controls using flow cytometry. Levels of soluble PD-1 and PD-L1 were also compared using commercially available ELISA kits. Results Expression of PD-1 and PD-L1 was higher on all lymphocyte subsets in patients with sepsis compared to controls (p < 0.05). PD-L2 expression on CD27+ B cells was also higher in patients with sepsis (p = 0.0317). There was differential expression of PD-1 by CD27 status, with expression being higher in the B and T cell subsets associated with memory status (CD27+ and CD27-, respectively; p < 0.001). Higher PD-1 and PD-L1 expression was not associated with mortality or with a higher risk of nosocomial infection. There were no differences in levels of soluble PD-1 or PD-L1 between patients with sepsis and controls. Conclusions Higher expression of PD-1 by memory subpopulations of B cells and CD4+ T cells, with normal soluble PD-1 and PD-L1 in patients with sepsis, are novel findings. This information may be useful to enrich sepsis populations for trials of PD-1/PD-L1 blockade.

Type: Article
Title: Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s13054-018-2020-2
Publisher version: https://doi.org/10.1186/s13054-018-2020-2
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Life Sciences & Biomedicine, Critical Care Medicine, General & Internal Medicine, Sepsis, Septic shock, Programmed death-1, Enrichment, Outcomes, MEMORY B-CELLS, CRITICAL-CARE, SEPTIC SHOCK, CLASSIFICATION, DEFINITIONS, SEVERITY
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Internal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10049293
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