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, 21 (1), 186

Monocyte Programmed Death ligand-1 Expression Is an Early Marker for Predicting Infectious Complications in Acute Pancreatitis

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Monocyte Programmed Death ligand-1 Expression Is an Early Marker for Predicting Infectious Complications in Acute Pancreatitis

Tingting Pan et al. Crit Care.

Abstract

Background: Acute pancreatitis (AP) is a life-threatening disease that requires early identification of patients at risk of developing infectious complications. Immunosuppression is an initial event that is key to AP pathogenesis. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) system is reported to mediate evasion of host immune surveillance in many diseases; however, the relationship between PD-1/PD-L1 expression and these parameters or infectious complications in AP has not been elucidated. This study was conducted to determine whether PD-1 and PD-L1 are upregulated and to reveal the relationship between PD-1/PD-L1 expression and the development of infectious complications in AP.

Methods: Sixty-three patients with AP and 32 sex- and age-matched healthy control subjects were prospectively enrolled. On days 1 and 3 after the onset of AP, we measured PD-1 expression in peripheral CD4+ T cells and PD-L1 and human leukocyte antigen-DR (HLA-DR) expression in CD14+ monocytes using flow cytometry. Plasma interleukin (IL)-10 levels were measured by enzyme-linked immunosorbent assay.

Results: Compared with healthy volunteers, the percentages of PD-1-expressing CD4+ lymphocytes and PD-L1-expressing CD14+ monocytes were increased in patients with AP on days 1 and 3 after onset, especially those with infectious complications. Moreover, increased PD-1/PD-L1 expression was associated with increased occurrence of infectious complications, decreased circulating lymphocytes, and increased plasma IL-10 concentration. Multivariate regression analysis indicated that the increased percentage of PD-L1-expressing CD14+ monocytes was an independent risk factor for infectious complications in AP. Area under the ROC curve analysis showed the combination of Acute Physiology and Chronic Health Evaluation II score and PD-L1 and HLA-DR expression in CD14+ monocytes had high accuracy in predicting infectious complications in patients with AP.

Conclusions: The PD-1/PD-L1 system plays an essential role in the early immunosuppression of AP. PD-L1 expression in CD14+ monocytes may be a new marker for predicting risk of infectious complications in patients with AP.

Keywords: Acute pancreatitis; Immunosuppression; Infection; PD-L1; Prediction.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the Ruijin Hospital Ethics Committee of Shanghai Jiaotong University School of Medicine, China. Formal informed consent was obtained from the patients or their next of kin.

Consent for publication

Consent for publication was obtained from the patients or their next of kin.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

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

Figures

Fig. 1
Fig. 1
Programmed cell death 1 (PD-1) expression in CD4+ lymphocytes and programmed cell death ligand 1 (PD-L1) expression in CD14+ monocytes in patients with acute pancreatitis (AP). a PD-1 expression in circulating CD4+ lymphocytes and b PD-L1 and c human leukocyte antigen (HLA)-DR expression in CD14+ monocytes were measured in whole blood from healthy control subjects (HC, n = 32) and patients with AP (n = 63) on day 1 (D1) and day 3 (D3) after disease onset. Results are presented as percentages of positive cells among the total population of CD14+ monocytes or CD4+ lymphocytes. d Representative PD-1 expression levels in CD4+ lymphocytes and e PD-L1 and f HLA-DR expression in CD14+ monocytes. Values in the upper right quadrant indicate the percentage of cells that express PD-1, PD-L1, or HLA-DR. *P < 0.05 compared with healthy controls. **P < 0.01 compared with healthy controls
Fig. 2
Fig. 2
Receive operating characteristic (ROC) curve for predicting infectious complications in patients with AP. APACHE Acute Physiology and Chronic Health Evaluation, HLA-DR Human leukocyte antigen-DR, PD-L1 Programmed cell death receptor ligand-1

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