Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study
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...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2018-04-01
|
Series: | Critical Care |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s13054-018-2020-2 |
id |
doaj-73391f1c17804f3eaa4e1a95c67a8854 |
---|---|
record_format |
Article |
spelling |
doaj-73391f1c17804f3eaa4e1a95c67a88542020-11-24T21:11:53ZengBMCCritical Care1364-85352018-04-012211710.1186/s13054-018-2020-2Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot studyJulie K. Wilson0Yuan Zhao1Mervyn Singer2Jo Spencer3Manu Shankar-Hari4Department of Intensive Care Medicine, Guy’s and St Thomas’ Hospitals NHS Foundation TrustDepartment of Immunobiology, School of Immunology & Microbial Sciences, King’s College LondonBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College LondonDepartment of Immunobiology, School of Immunology & Microbial Sciences, King’s College LondonDepartment of Intensive Care Medicine, Guy’s and St Thomas’ Hospitals NHS Foundation TrustAbstract 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.http://link.springer.com/article/10.1186/s13054-018-2020-2SepsisSeptic shockProgrammed death-1EnrichmentOutcomes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julie K. Wilson Yuan Zhao Mervyn Singer Jo Spencer Manu Shankar-Hari |
spellingShingle |
Julie K. Wilson Yuan Zhao Mervyn Singer Jo Spencer Manu Shankar-Hari Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study Critical Care Sepsis Septic shock Programmed death-1 Enrichment Outcomes |
author_facet |
Julie K. Wilson Yuan Zhao Mervyn Singer Jo Spencer Manu Shankar-Hari |
author_sort |
Julie K. Wilson |
title |
Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study |
title_short |
Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study |
title_full |
Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study |
title_fullStr |
Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study |
title_full_unstemmed |
Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study |
title_sort |
lymphocyte subset expression and serum concentrations of pd-1/pd-l1 in sepsis - pilot study |
publisher |
BMC |
series |
Critical Care |
issn |
1364-8535 |
publishDate |
2018-04-01 |
description |
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. |
topic |
Sepsis Septic shock Programmed death-1 Enrichment Outcomes |
url |
http://link.springer.com/article/10.1186/s13054-018-2020-2 |
work_keys_str_mv |
AT juliekwilson lymphocytesubsetexpressionandserumconcentrationsofpd1pdl1insepsispilotstudy AT yuanzhao lymphocytesubsetexpressionandserumconcentrationsofpd1pdl1insepsispilotstudy AT mervynsinger lymphocytesubsetexpressionandserumconcentrationsofpd1pdl1insepsispilotstudy AT jospencer lymphocytesubsetexpressionandserumconcentrationsofpd1pdl1insepsispilotstudy AT manushankarhari lymphocytesubsetexpressionandserumconcentrationsofpd1pdl1insepsispilotstudy |
_version_ |
1716752325358387200 |