Expression of mHLA-DR, CD39+ Treg and IL-10 in lung cancer patients with sepsis was correlated with the severity and prognosis of the disease

doi:10.3877/cma.j.issn.1674-6902.2023.02.004

Abstract

Abstract:

Objective

To study the value of peripheral monocyte HLA-DR, peripheral blood CD39⁺ Tregs and IL-10 expression in evaluating the state and prognosis of patients with lung cancer complicated with sepsis.

Methods

A total of 68 patients with lung cancer complicated by sepsis who were hospitalized in our hospital from September 2020 to December 2021 were selected and divided into sepsis divided into sepsis group 38 cases, septic shock group 30 cases, lung cancer without sepsis group 36 cases. The levels of mHLA-DR, CD39⁺ Treg and IL-10 in peripheral monocytes were measured after admission. The correlation between the three indexes and the severity was analyzed. ROC curve was used to analyze the three indexes and the ability of combined detection to evaluate the severity and prognosis of sepsis.

Results

① The proportion of CD39⁺ Treg and IL-10 level in lung cancer patients with sepsis were significantly higher than those in non-sepsis group (3.92±1.35 vs. 2.14±0.86%), (37.08±5.32 vs. 9.22±1.75 pg/ml) (P<0.01). The mHLA-DR level was lower than that in non-sepsis group and control group 7 days before infection (P<0.01). HLA-DR decreased to the lowest level in sepsis group on the 7 th day after admission, which was significantly different from that at admission (91.07±1.14 vs. 84.59±0.7%) (P<0.01). The proportion of CD39⁺ Treg and IL-10 levels were higher than those in the survival group (P<0.01); ③Multivariate logistic regression analysis in the lung cancer sepsis group showed that ΔHLA-DR7 (OR=2.195, P<0.001), CD39⁺ Treg (OR=2.853, P=0.015), IL-10 (OR=1.868, P=0.002) and APACHE Ⅱ and SOFA scores were independent risk factors for poor prognosis of sepsis; ④ The area under the curve of ΔHLA-DR7 in evaluating the prognosis of sepsis was 0.911, and when the cutoff value was 8.7%, the sensitivity was 89.28% and the specificity was 97.6%) was greater than that of CD39⁺ Treg and IL-10, and the difference was statistically significant (P<0.01).

Conclusion

ΔHLA-DR 7 is a good index for evaluating the severity and prognosis of lung cancer with sepsis. ΔHLA-DR7 combined with CD39⁺ Treg and IL-10 can significantly improve the diagnosis and prognosis of sepsis.

Key words: mHLA-DR, CD39⁺ Tregs, Interleukin-10, Bronchogenic carcinoma, Sepsis

Ning Zhang, Mingming Zhou, Zhengying Jiang, Guixin Wu, Qikun Lyu. Expression of mHLA-DR, CD39⁺ Treg and IL-10 in lung cancer patients with sepsis was correlated with the severity and prognosis of the disease[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(02): 169-174.

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References 30

1	Taccone FS, Artigas AA, Sprung CL, et al. Characteristics and outcomes of cancer patients in European ICUs[J]. Crit Care, 2009, 13(1): R15.
2	Vandijck DM, Benoit DD, Depuydt PO, et al. Impact of recent intravenous chemotherapy on outcome in severe sepsis and septic patients with cancer and sepsis 307 shock patients with hematological malignancies[J]. Intensive Care Med, 2008, 34(5): 847-855.
3	Hampshire PA, Welch CA, McCrossan LA, et al. Admission factors associated with hospital mortality in patients with haematological malignancy admitted to UK adult, general critical care units: a secondary analysis of the ICNARC Case Mix Programme Database[J]. Crit Care, 2009, 13(4): R137.
4	Tolsma V, Schwebel C, Azoulay E, et al. Sepsis severe or septic shock: outcome according to immune status and immunodeficiency profile[J]. Chest, 2014, 146(5): 1205-1213.
5	Yin J, Chen Y, Huang JL, et al. Prognosis-related classification and dynamic monitoring of immune status in patients with sepsis: A prospective observational study[J]．World J Emerg Med, 2021, 12(3): 185-191.
6	Vuk-Pavlovic S. Rebuilding immunity in cancer patients[J]. Blood Cells Mol Dis, 2008, 40(1): 94-100.
7	Zanza C, Caputo G, Tornatore G, et al. Cellular immuno-profile in septic human host: A scoping review[J]. Biology (Basel), 2022, 11(11): 1626.
8	Mirouse A, Vigneron C, Llitjos JF, et al. Sepsis and cancer: An interplay of friends and foes[J]. Am J Respir Crit Care Med, 2020, 202(12): 1625-1635.
9	Peters van Ton AM, Kox M, Abdo WF, et al. Precision immunotherapy for sepsis[J]. Front Immunol, 2018, 9: 1926.
10	Fumeaux T, Pugin J. Is the measurement of monocytes HLA-DR expression useful in patient with sepsis[J]. Intensive Care Med, 2006, 32(8): 1106-1108.
11	Zhuang YG, Peng H, Chen YZ, et al. Dynamic monitoring of monocyte HLA-DR expression for the diagnosis, prognosis, and prediction of sepsis[J]. Front Biosci (Landmark Ed), 2017, 22(8): 1344-1354.
12	Tschaikowsky K, Hedwig-Geissing M, Schiele A, et al. Coincidence of pro- and anti-inflammatory responses in the early phase of severe sepsis: Longitudinal study of mononuclear histocompatibility leukocyte antigen-DR expression, procalcitonin, C-reactive protein, and changes in T-cell subsets in septic and postoperative patients[J]. Crit Care Med, 2002, 30(5): 1015-1023.
13	Le Tulzo Y, Pangault C, Amiot L, et al. Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock[J]. Am J Respir Crit Care Med, 2004, 169(10): 1144-1151.
14	Pangault C, Le Tulzo Y, Tattevin P, et al. Down-modulation of granulocyte macrophage-colony stimulating factor receptor on monocytes during human septic shock[J]. Rit Care Med, 2006, 34(4): 1193-1201.
15	Winkler MS, Rissiek A, Priefler M, et al. Human leucocyte antigen (HLA-DR) gene expression is reducedin sepsis and correlates with impaired TNF-αresponse: A diagnostic tool for immunosuppression？[J]. PLoS One, 2017, 12(8): e0182427.
16	Becker C, Kubach J, Wijdenes J, et al. CD4-mediated functional activation of human CD4+CD25+ regulatory T cells[J]. Eur J Immunol, 2007, 37(5): 1217-1223.
17	Wachstein J, Tischer S, Figueiredo C, et al. HSP70 enhances immunosuppressive function of CD4(+)CD25(+)FoxP3(+) T regulatory cells and cytotoxicity in CD4(+)CD25(-) T cells[J]. PLoS One, 2012, 7(12): e51747.
18	Wang L, Xie Y, Zhu LJ, et al. An association between immunosenescence and CD4(+)CD25(+) regulatory T cells: a systematic review[J]. Biomed Environ Sci, 2010, 23(4): 327-232.
19	Tiemessen MM, Jagger AL, Evans HG, et al. CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages[J]. Proc Natl Acad Sci U S A, 2007, 104(49): 19446-19451.
20	Borsellino G, Kleinewietfeld M, DiMitri D, et al. Expression of ectonucleotidase CD39 by Foxp3+Treg cells: hydrolysis of extracellular ATP and immune suppression[J]. Blood, 2007, 110(4): 1225-1232.
21	Liu J, Shi K, Chen M, et al. Elevated miR-155 expression induces immunosuppression via CD39(+) regulatory T-cells in sepsis patient[J]. Int J Infect Dis, 2015, 40: 135-141.
22	Huang H, Xu R, Lin F, et al. Highcirculating CD39(+) regulatory T cells predict poorsurvival for sepsis patients[J]. Int J Infect Dis, 2015, 30: 57-63.
23	Dimitrov E, Enchev E, Minkov G, et al. Outcome could be predicted by lower monocyte human leukocyte antigen-DR expression in patients with complicated intra-abdominal infections: A review. [J]. Surg Infect, 2020, 21(2): 77-80.
24	Mokart D, Textoris J, Chow-Chine L, et al. HLA-DR and B7-2 (CD86) monocyte expressions after major cancer surgery: profile in sepsis[J]. Minerva Anestesiol, 2011, 77(5): 522-527.
25	Li L, Chen L, Lin F, et al. Study of the expression of inflammatory factors IL-4, IL-6, IL-10, and IL-17 in liver failure complicated by coagulation dysfunction and sepsis[J]. J Inflamm Res, 2021, 14: 1447-1453.
26	Gogos CA, Drosou E, Bassaris HP, et al. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options[J]. J Infect Dis, 2000, 181(1): 176-180.
27	Zhang W, Wang W, Hou W, et al. The diagnostic utility of IL-10, IL-17, and PCT in patients with sepsis infection[J]. Front Public Health, 2022, 10: 923457.
28	Hynninen M, Pettil V, Takkunen O, et al. Predictive value of monocyte histocompatibility leukocyte antigen-DR expression and plasma interleukin-4 and -10 levels in critically ill patients with sepsis[J]. Shock, 2003, 20(1): 1-4.
29	Wang S, Li T, Li Y, et al. Predictive value of four different scoring systems for septic patient′s outcome: a retrospective analysis with 311 patients[J]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 2017, 29(2): 133-138.
30	Nathan N, Sculier JP, Ameye L, et al. Sepsis and septic shock definitions in patients with cancer admitted in ICU[J]. J Intensive Care Med, 2021, 36(3): 255-261.

组　别	入院时mHLA-DR	入院第3天mHLA-DR	入院第7天mHLA-DR	mHLA-DR3(%)(第3天-第0日差值)	mHLA-DR7(%)(第7天-第0日差值)	CD39⁺ Tregs(%)	IL-10(pg/ml)
脓毒症组	91.07±1.14^a	87.07±1.22^a	84.59±0.75^ac	4.78±0.61	7.53±1.22^a	3.92±1.35^a	37.08±5.32^a
脓毒症休克组	88.09±1.02^a	84.53±0.98^a	76.24±0.61^ac	6.12±0.49	9.87±1.39^a	5.33±1.81^a	58.76±7.29^ab
对照组	95.07±0.86	94.38±0.99	96.14±1.22	0.96±0.05	0.83±0.08	2.14±0.86	9.22±1.75

组　别	入院时mHLA-DR	入院第3天mHLA-DR	入院第7天mHLA-DR	mHLA-DR3(%)(第3天-第0日差值)	mHLA-DR7(%)(第7天-第0日差值)	CD39⁺ Tregs(%)	IL-10(pg/ml)
脓毒症组	91.07±1.14^a	87.07±1.22^a	84.59±0.75^ac	4.78±0.61	7.53±1.22^a	3.92±1.35^a	37.08±5.32^a
脓毒症休克组	88.09±1.02^a	84.53±0.98^a	76.24±0.61^ac	6.12±0.49	9.87±1.39^a	5.33±1.81^a	58.76±7.29^ab
对照组	95.07±0.86	94.38±0.99	96.14±1.22	0.96±0.05	0.83±0.08	2.14±0.86	9.22±1.75

临床资料	生存者(n＝46)	死亡者(n＝22)	统计量	P值
年龄(岁)	58.2±6.4	63.9±7.5	2.658	0.266
性别(男/女，n)	21/25	16/6	4.401^c	0.412
脓毒症分级(n)			4.319^a	0.000
脓毒症	30	8
脓毒症休克	8	12
第7天HLA-DR(%)	86.72±0.59	75.69±0.64	17.410	0.010
ΔHLA-DR3(%)	5.89±0.53	6.51±0.40	2.856	0.171
ΔHLA-DR7(%)	7.86±0.47	9.07±0.32	12.115	0.000
CD39⁺ Treg(%)	4.16±1.19	6.08±2.15^b	1.112	0.000
IL-10(pg/ml)	31.39±4.78	62.15±8.34^a	7.319	0.000
APACHEⅡ评分(分)	19.02±4.11	28.56±6.91^b	8.356	0.000
SOFA评分(分)	3.42±1.75	6.63±5.86^a	5.024	0.000

临床资料	生存者(n＝46)	死亡者(n＝22)	统计量	P值
年龄(岁)	58.2±6.4	63.9±7.5	2.658	0.266
性别(男/女，n)	21/25	16/6	4.401^c	0.412
脓毒症分级(n)			4.319^a	0.000
脓毒症	30	8
脓毒症休克	8	12
第7天HLA-DR(%)	86.72±0.59	75.69±0.64	17.410	0.010
ΔHLA-DR3(%)	5.89±0.53	6.51±0.40	2.856	0.171
ΔHLA-DR7(%)	7.86±0.47	9.07±0.32	12.115	0.000
CD39⁺ Treg(%)	4.16±1.19	6.08±2.15^b	1.112	0.000
IL-10(pg/ml)	31.39±4.78	62.15±8.34^a	7.319	0.000
APACHEⅡ评分(分)	19.02±4.11	28.56±6.91^b	8.356	0.000
SOFA评分(分)	3.42±1.75	6.63±5.86^a	5.024	0.000

临床资料	估计值	标准误	Wald值	OR值(95%CI)	P值
年龄	0.009	0.012	0.512	1.723(0.549~2.897)	0.012
性别	0.678	0.329	3.162	2.949(0.915~4.982)	0.182
HLA-DR (第0天)	－2.276	1.942	1.374	0.103(0.002~4.616)	0.241
HLA-DR (第3天)	－3.404	2.692	1.599	0.033(0.000~6.502)	0.206
HLA-DR (第7天)	－0.452	1.801	0.063	0.953(0.046~1.859)	0.086
ΔHLA-DR3	1.877	2.261	0.689	0.153(0.02~12.867)	0.406
ΔHLA-DR7	1.658	0.001	14.247	0.169(0.054~0.283)	0.001
CD39⁺ Tregs	0.217	0.045	2.336	1.240(0.941~1.634)	0.006
IL-10	0.164	0.034	3.391	1.068(0.973~1.166)	0.017
APACHEⅡ	0.218	0.042	8.870	2.860(1.693~4.027)	0.000
SOFA	0.674	0.168	15.114	2.008(0.765~3.941)	0.000

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