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. 2018 Apr 17;22(1):95.
doi: 10.1186/s13054-018-2020-2.

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

Julie K Wilson  1 , Yuan Zhao  2 , Mervyn Singer  3 , Jo Spencer  2 , Manu Shankar-Hari  4
Affiliations

"VSports在线直播" Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study

Julie K Wilson et al. Crit Care. .

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 VSports手机版. 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 V体育安卓版. 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) V体育ios版. 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. VSports最新版本.

Keywords: Enrichment; Outcomes; Programmed death-1; Sepsis; Septic shock. V体育平台登录.

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"VSports app下载" Conflict of interest statement

Ethics approval and consent to participate

All patients who met the eligibility criteria were consented prior to blood sampling VSports注册入口. Ethics approval for the study was given by HRA Research Ethics Committee London (Camberwell St Giles) Address: East of England REC Centre Victoria House, Capital Park Fulbourn, Cambridge CB21 5XB. Approval reference: 12/LO/0326.

Competing interests

MS is on the steering committee for a clinical trial of anti PD-L1 therapy in sepsis V体育官网入口. The other authors have no competing interests to declare.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) expression on B cells. a-c Comparison of the mean fluorescence intensity (MFI) of PD-1, PD-L1 and PD-L2 on B cells in patients with sepsis compared with healthy controls. d-f Comparison of the MFI of PD-1, PD-L1 and PD-L2 between CD27+ B cells and CD27- B cells within patients with sepsis. The boxes below show the corresponding proportion of positive cells for each comparison, with corresponding p values. *Significant p values
Fig. 2
Fig. 2
Programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) expression on CD4+ T cells. a-c Comparison of the mean fluorescence intensity (MFI) of PD-1, PD-L1 and PD-L2 on T cells in patients with sepsis compared with healthy controls. d-f Comparison of the MFI of PD-1, PD-L1 and PD-L2 between CD27+ T cells and CD27- T cells within patients with sepsis. The boxes below show the corresponding proportion of positive cells for each comparison, with corresponding p values. *Significant p values
See this image and copyright information in PMC

References (VSports)

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