Over-expression of programmed death-ligand 1 and programmed death-1 on antigen-presenting cells as a predictor of organ dysfunction and mortality during early sepsis: a prospective cohort study

doi:10.5847/wjem.j.1920-8642.2023.041

Abstract

Abstract:

BACKGROUND: This study aimed to explore the changes of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) expression on antigen-presenting cells (APCs) and evaluate their association with organ failure and mortality during early sepsis.

METHODS: In total, 40 healthy controls and 198 patients with sepsis were included in this study. Peripheral blood was collected within the first 24 h after the diagnosis of sepsis. The expression of PD-L1 and PD-1 was determined on APCs, such as B cells, monocytes, and dendritic cells (DCs), by flow cytometry. Cytokines in plasma, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, and IL-17A were determined by Luminex assay.

RESULTS: PD-1 expression decreased significantly on B cells, monocytes, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) as the severity of sepsis increased. PD-1 expression was also markedly decreased in non-survivors compared with survivors. In contrast, PD-L1 expression was markedly higher on mDCs, pDCs, and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors. The PD-L1 expression on APCs (monocytes and DCs) was weakly related to organ dysfunction and inflammation. The area under the receiver operating characteristic curve (AUC) of the PD-1 percentage of monocytes (monocyte PD-1%)+APACHE II model (0.823) and monocyte PD-1%+SOFA model (0.816) had higher prognostic value than other parameters alone. Monocyte PD-1% was an independent risk factor for 28-day mortality.

CONCLUSION: The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs. PD-L1 in monocytes and DCs was weakly correlated with inflammation and organ dysfunction during early sepsis. The combination of SOFA or APACHE II scores with monocyte PD-1% could improve the prediction ability for mortality.

Key words: Inflammation, Programmed death-ligand 1, Programmed death-1, Antigen-presenting cells

Jia-bao Li, Miao-rong Xie, Mei-li Duan, Ya-nan Yu, Chen-chen Hang, Zi-ren Tang, Chun-sheng Li. Over-expression of programmed death-ligand 1 and programmed death-1 on antigen-presenting cells as a predictor of organ dysfunction and mortality during early sepsis: a prospective cohort study[J]. World Journal of Emergency Medicine, 2023, 14(3): 179-185.

Figures/Tables 4

Table 1.

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Characteristics	Healthy control (n=40)	Overall sepsis (n=198)	P-value (control vs. overall)
Age, years	68 (57-74)	71 (56-80)	0.389
Male/Female	20/20	111/87	0.121
White blood cell count, ×10⁹	5.81 (4.85-6.52)	12.83 (8.00-19.28)	<0.001
Neutrophil percentage, %	56.25 (48.03-63.33)	88.55 (81.98-92.75)	<0.001
Neutrophil count, ×10⁹	4.70 (3.62-5.65)	11.59 (7.08-17.69)	<0.001
Lymphocyte percentage, %	2.30 (1.70-2.70)	6.10 (3.30-11.13)	<0.001
Lymphocyte count, ×10⁹	2.12 (1.74-2.36)	0.77 (0.48-1.14)	<0.001
Monocyte count, ×10⁹	0.29 (0.27-0.38)	0.56 (0.28-0.98)	<0.001
Lactate, mmol/L	1.00 (0.60-1.38)	1.95 (1.30-3.23)	<0.001
SOFA score	0 (0-1)	7 (4-10)	<0.001
APACHE Ⅱ score	1 (0-2)	15 (10-21)	<0.001
Comorbidity more than one	0	140 (70.7)	<0.001
Primary infection sites
Respiratory infection		105 (53.0)	-
Intra-abdominal infection		47 (23.7)	-
Cerebral infection		19 (9.6)	-
Urinary infection		22 (11.1)	-
Others		5 (2.5)	-

Characteristics	Sepsis (n=121)	Septic shock (n=77)	P-value
Age, years	72 (55-82)	70 (56-79)	0.412
Male/Female	71/50	40/37	0.232
White blood cell count, ×10⁹	13.02 (9.02-18.68)	11.74 (7.59-23.79)	0.640
Neutrophil percentage, %	87.90 (81.95-91.50)	90.30 (81.55-94.05)	0.087
Neutrophil count, ×10⁹	11.80 (7.87-16.93)	11.41 (6.54-20.90)	0.915
Lymphocyte percentage, %	6.40 (3.45-11.05)	5.00 (3.15-12.70)	0.384
Lymphocyte count, ×10⁹	0.82 (0.52-1.20)	0.65 (0.39-1.09)	0.236
Monocyte count, ×10⁹	0.67 (0.38-1.00)	0.45 (0.19-0.74)	0.004
Lactate, mmol/L	1.60 (1.15-2.25)	2.90 (1.72-6.70)	<0.001
SOFA score	5 (3-7)	10 (8-12)	<0.001
APACHE Ⅱ score	13 (8-17)	19 (14-26)	<0.001
28-day mortality	30 (24.8)	40 (51.9)	<0.001
Comorbidity more than one	78 (64.5)	62 (80.5)	0.853
Primary infection sites
Respiratory infection	68 (56.2)	37 (48.1)	0.263
Intra-abdominal infection	27 (22.3)	20 (26.0)	0.555
Cerebral infection	12 (9.9)	7 (9.1)	0.847
Urinary infection	11 (9.1)	11 (14.3)	0.257
Others	3 (2.5)	2 (2.6)	0.959