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

Research output: Contribution to journalArticle

Julie K. Wilson, Yuan Zhao, Mervyn Singer, Jo Spencer, Manu Shankar-Hari

Original languageEnglish
JournalCRITICAL CARE
DOIs
Publication statusPublished - 17 Apr 2018

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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 cancer patients, 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 sepsis patients and controls; to characterize serum levels of PD-1 and PD-L1 in sepsis patients 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 sepsis patients (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 sepsis patients compared to controls (p<0.05). PD-L2 expression on CD27+ B cells was also higher in sepsis patients (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 nor with a higher risk of nosocomial infections. There were no differences in levels of soluble PD-1 or PD-L1 between sepsis patients 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 sepsis patients, are novel findings. This information may be useful to enrich sepsis populations for trials of PD-1/PD-L1 blockade.

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