Skip to main content
Top
Published in: Critical Care 1/2017

Open Access 01-12-2017 | Research

Monocyte programmed death ligand-1 expression is an early marker for predicting infectious complications in acute pancreatitis

Authors: Tingting Pan, Tianyun Zhou, Lei Li, Zhaojun Liu, Ying Chen, Enqiang Mao, Meiling Li, Hongping Qu, Jialin Liu

Published in: Critical Care | Issue 1/2017

Login to get access

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.
Literature
2.
go back to reference Gomatos IP, Xiaodong X, Ghaneh P, Halloran C, Raraty M, Lane B, et al. Prognostic markers in acute pancreatitis. Expert Rev Mol Diagn. 2014;14(3):333–46.CrossRefPubMed Gomatos IP, Xiaodong X, Ghaneh P, Halloran C, Raraty M, Lane B, et al. Prognostic markers in acute pancreatitis. Expert Rev Mol Diagn. 2014;14(3):333–46.CrossRefPubMed
3.
go back to reference Banks PA, Freeman ML. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006;101(10):2379–400.CrossRefPubMed Banks PA, Freeman ML. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006;101(10):2379–400.CrossRefPubMed
4.
go back to reference Buddingh KT, Koudstaal LG, van Santvoort HC, Besselink MG, Timmer R, Rosman C, et al. Early angiopoietin-2 levels after onset predict the advent of severe pancreatitis, multiple organ failure, and infectious complications in patients with acute pancreatitis. J Am Coll Surg. 2014;218(1):26–32.CrossRefPubMed Buddingh KT, Koudstaal LG, van Santvoort HC, Besselink MG, Timmer R, Rosman C, et al. Early angiopoietin-2 levels after onset predict the advent of severe pancreatitis, multiple organ failure, and infectious complications in patients with acute pancreatitis. J Am Coll Surg. 2014;218(1):26–32.CrossRefPubMed
5.
go back to reference Gloor B, Muller CA, Worni M, Martignoni ME, Uhl W, Buchler MW. Late mortality in patients with severe acute pancreatitis. Br J Surg. 2001;88(7):975–9.CrossRefPubMed Gloor B, Muller CA, Worni M, Martignoni ME, Uhl W, Buchler MW. Late mortality in patients with severe acute pancreatitis. Br J Surg. 2001;88(7):975–9.CrossRefPubMed
6.
go back to reference Li JP, Yang J, Huang JR, Jiang DL, Zhang F, Liu MF, et al. Immunosuppression and the infection in patients with early SAP. Front Biosci (Landmark Ed). 2013;18:892–900.CrossRef Li JP, Yang J, Huang JR, Jiang DL, Zhang F, Liu MF, et al. Immunosuppression and the infection in patients with early SAP. Front Biosci (Landmark Ed). 2013;18:892–900.CrossRef
7.
go back to reference Oiva J, Mustonen H, Kylanpaa ML, Kyhala L, Kuuliala K, Siitonen S, et al. Acute pancreatitis with organ dysfunction associates with abnormal blood lymphocyte signaling: controlled laboratory study. Crit Care. 2010;14(6):R207.CrossRefPubMedPubMedCentral Oiva J, Mustonen H, Kylanpaa ML, Kyhala L, Kuuliala K, Siitonen S, et al. Acute pancreatitis with organ dysfunction associates with abnormal blood lymphocyte signaling: controlled laboratory study. Crit Care. 2010;14(6):R207.CrossRefPubMedPubMedCentral
8.
go back to reference Oiva J, Mustonen H, Kylänpää ML, Kyhälä L, Alanärä T, Aittomäki S, et al. Patients with acute pancreatitis complicated by organ failure show highly aberrant monocyte signaling profiles assessed by phospho-specific flow cytometry. Crit Care Med. 2010;38(8):1702–8.CrossRefPubMed Oiva J, Mustonen H, Kylänpää ML, Kyhälä L, Alanärä T, Aittomäki S, et al. Patients with acute pancreatitis complicated by organ failure show highly aberrant monocyte signaling profiles assessed by phospho-specific flow cytometry. Crit Care Med. 2010;38(8):1702–8.CrossRefPubMed
9.
go back to reference Pietruczuk M, Dabrowska MI, Wereszczynska-Siemiatkowska U, Dabrowski A. Alteration of peripheral blood lymphocyte subsets in acute pancreatitis. World J Gastroenterol. 2006;12(33):5344–51.CrossRefPubMedPubMedCentral Pietruczuk M, Dabrowska MI, Wereszczynska-Siemiatkowska U, Dabrowski A. Alteration of peripheral blood lymphocyte subsets in acute pancreatitis. World J Gastroenterol. 2006;12(33):5344–51.CrossRefPubMedPubMedCentral
10.
go back to reference Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.CrossRefPubMed Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.CrossRefPubMed
11.
go back to reference Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007;27(1):111–22.CrossRefPubMedPubMedCentral Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007;27(1):111–22.CrossRefPubMedPubMedCentral
12.
go back to reference Yokoyama S, Miyoshi H, Nakashima K, Shimono J, Hashiguchi T, Mitsuoka M, et al. Prognostic value of programmed death ligand 1 and programmed death 1 expression in thymic carcinoma. Clin Cancer Res. 2016;22(18):4727–34.CrossRefPubMed Yokoyama S, Miyoshi H, Nakashima K, Shimono J, Hashiguchi T, Mitsuoka M, et al. Prognostic value of programmed death ligand 1 and programmed death 1 expression in thymic carcinoma. Clin Cancer Res. 2016;22(18):4727–34.CrossRefPubMed
13.
go back to reference Guignant C, Lepape A, Huang X, Kherouf H, Denis L, Poitevin F, et al. Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients. Crit Care. 2011;15(2):R99.CrossRefPubMedPubMedCentral Guignant C, Lepape A, Huang X, Kherouf H, Denis L, Poitevin F, et al. Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients. Crit Care. 2011;15(2):R99.CrossRefPubMedPubMedCentral
14.
go back to reference Tenner S, Baillie J, DeWitt J, Vege SS. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013;108(9):1400–15.CrossRefPubMed Tenner S, Baillie J, DeWitt J, Vege SS. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013;108(9):1400–15.CrossRefPubMed
15.
go back to reference Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102–11.CrossRefPubMed Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102–11.CrossRefPubMed
16.
go back to reference Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371(9613):651–9.CrossRefPubMed Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371(9613):651–9.CrossRefPubMed
17.
go back to reference Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K, et al. IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br J Cancer. 2015;112(9):1501–9.CrossRefPubMedPubMedCentral Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K, et al. IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br J Cancer. 2015;112(9):1501–9.CrossRefPubMedPubMedCentral
18.
go back to reference Chang K, Svabek C, Vazquez-Guillamet C, Sato B, Rasche D, Wilson S, et al. Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis. Crit Care. 2014;18(1):R3.CrossRefPubMedPubMedCentral Chang K, Svabek C, Vazquez-Guillamet C, Sato B, Rasche D, Wilson S, et al. Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis. Crit Care. 2014;18(1):R3.CrossRefPubMedPubMedCentral
19.
go back to reference Zhang Y, Zhou Y, Lou J, Li J, Bo L, Zhu K, et al. PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction. Crit Care. 2010;14(6):R220.CrossRefPubMedPubMedCentral Zhang Y, Zhou Y, Lou J, Li J, Bo L, Zhu K, et al. PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction. Crit Care. 2010;14(6):R220.CrossRefPubMedPubMedCentral
20.
go back to reference Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2(3):261–8.CrossRefPubMed Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2(3):261–8.CrossRefPubMed
21.
go back to reference Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, et al. Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nat Med. 2010;16(4):452–9.CrossRefPubMedPubMedCentral Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, et al. Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nat Med. 2010;16(4):452–9.CrossRefPubMedPubMedCentral
22.
go back to reference Huang A, Zhang B, Yan W, Wang B, Wei H, Zhang F, et al. Myeloid-derived suppressor cells regulate immune response in patients with chronic hepatitis B virus infection through PD-1-induced IL-10. J Immunol. 2014;193(11):5461–9.CrossRefPubMed Huang A, Zhang B, Yan W, Wang B, Wei H, Zhang F, et al. Myeloid-derived suppressor cells regulate immune response in patients with chronic hepatitis B virus infection through PD-1-induced IL-10. J Immunol. 2014;193(11):5461–9.CrossRefPubMed
23.
go back to reference Shao R, Fang Y, Yu H, Zhao L, Jiang Z, Li CS. Monocyte programmed death ligand-1 expression after 3-4 days of sepsis is associated with risk stratification and mortality in septic patients: a prospective cohort study. Crit Care. 2016;20(1):124.CrossRefPubMedPubMedCentral Shao R, Fang Y, Yu H, Zhao L, Jiang Z, Li CS. Monocyte programmed death ligand-1 expression after 3-4 days of sepsis is associated with risk stratification and mortality in septic patients: a prospective cohort study. Crit Care. 2016;20(1):124.CrossRefPubMedPubMedCentral
24.
go back to reference Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306(23):2594–605.CrossRefPubMedPubMedCentral Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306(23):2594–605.CrossRefPubMedPubMedCentral
25.
go back to reference Kubo T, Ono S, Miyazaki H, Saitoh D, Yamamoto J, Hase K. Perioperative programmed death 1 expression on CD4+ T cells predicts the incidence of postoperative infectious complications. Shock. 2015;44(4):323–9.CrossRefPubMed Kubo T, Ono S, Miyazaki H, Saitoh D, Yamamoto J, Hase K. Perioperative programmed death 1 expression on CD4+ T cells predicts the incidence of postoperative infectious complications. Shock. 2015;44(4):323–9.CrossRefPubMed
27.
go back to reference Volk HD, Waschke SR, Diezel W, Grunow R, von Baehr R, Fiebig H. Decrease of HLA-DR antigen expression by human monocytes during cultivation in absence of exogenous or endogenous interferon-γ. Immunol Lett. 1985;10(2):103–7.CrossRefPubMed Volk HD, Waschke SR, Diezel W, Grunow R, von Baehr R, Fiebig H. Decrease of HLA-DR antigen expression by human monocytes during cultivation in absence of exogenous or endogenous interferon-γ. Immunol Lett. 1985;10(2):103–7.CrossRefPubMed
28.
go back to reference Shen X, Sun J, Ke L, Zou L, Li B, Tong Z, et al. Reduced lymphocyte count as an early marker for predicting infected pancreatic necrosis. BMC Gastroenterol. 2015;15:147.CrossRefPubMedPubMedCentral Shen X, Sun J, Ke L, Zou L, Li B, Tong Z, et al. Reduced lymphocyte count as an early marker for predicting infected pancreatic necrosis. BMC Gastroenterol. 2015;15:147.CrossRefPubMedPubMedCentral
29.
go back to reference Ho YP, Sheen IS, Chiu CT, Wu CS, Lin CY. A strong association between down-regulation of HLA-DR expression and the late mortality in patients with severe acute pancreatitis. Am J Gastroenterol. 2006;101(5):1117–24.CrossRefPubMed Ho YP, Sheen IS, Chiu CT, Wu CS, Lin CY. A strong association between down-regulation of HLA-DR expression and the late mortality in patients with severe acute pancreatitis. Am J Gastroenterol. 2006;101(5):1117–24.CrossRefPubMed
30.
go back to reference Sachse C, Prigge M, Cramer G, Pallua N, Henkel E. Association between reduced human leukocyte antigen (HLA)-DR expression on blood monocytes and increased plasma level of interleukin-10 in patients with severe burns. Clin Chem Lab Med. 1999;37(3):193–8.CrossRefPubMed Sachse C, Prigge M, Cramer G, Pallua N, Henkel E. Association between reduced human leukocyte antigen (HLA)-DR expression on blood monocytes and increased plasma level of interleukin-10 in patients with severe burns. Clin Chem Lab Med. 1999;37(3):193–8.CrossRefPubMed
Metadata
Title
Monocyte programmed death ligand-1 expression is an early marker for predicting infectious complications in acute pancreatitis
Authors
Tingting Pan
Tianyun Zhou
Lei Li
Zhaojun Liu
Ying Chen
Enqiang Mao
Meiling Li
Hongping Qu
Jialin Liu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2017
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-017-1781-3

Other articles of this Issue 1/2017

Critical Care 1/2017 Go to the issue