Study on the correlation between serum soluble PD-1 and the severity and prognosis of pulmonary tuberculosis patients in ICU

doi:10.19983/j.issn.2096-8493.20250032

Abstract

Abstract:

Objective: To evaluate the value of serum soluble programmed death receptor-1 (PD)-1 in assessing prognosis of the patients with pulmonary tuberculosis (PTB) in intensive care unit (ICU). Methods: A total of 102 pulmonary tuberculosis patients admitted to the ICU of Hebei Provincial Chest Hospital from April 2022 to April 2024 were included in this study, and they were divided into survival group and death group respectively, according to their survival status after 28 days in ICU. The serum soluble PD-1 levels of the patients in the two groups were compared, and its correlation with the severity, prognosis score and nutritional indicator of pulmonary tuberculosis patients in ICU was analyzed. Receiver operating characteristic (ROC) curve analysis was used to analyze the value of serum soluble PD-1 in assessing prognosis of the patients with pulmonary tuberculosis in ICU. Results: Among the 102 pulmonary tuberculosis patients in ICU who were included in this study, 42 patients died (death group) with the case fatality rate of 41.2% (42/102), and 60 patients survived (survival group) with the survival rate of 58.8% (60/102). Compared with the patients in the survival group, the serum PD-1 level increased significantly among those patients in the death group (PD-1 (pg/ml): 47.25 (41.48, 51.15) vs. 35.45 (28.40, 41.80), Z=―6.399, P<0.001). PD-1 level was positively correlated with APACHE Ⅱ and SOFA scores (r=0.580, P<0.001; r=0.575, P<0.001), negatively correlated with prealbumin level (r=―0.297, P=0.002), and not correlated with lactate level (r=0.104, P=0.297). The results of ROC curve analysis showed that the area under the ROC curve (AUC) of PD-1 in predicting death of pulmonary tuberculosis patients after entering ICU 28 days was 0.873 (95%CI: 0.809-0.938). The optimal cutoff value of serum PD-1 was 38.45 pg/ml, with the sensitivity and the specificity were 95.2% and 65.0% respectively. While PD-1 value was combined with APACHE Ⅱ, the sensitivity was more than 99.9% and the specificity was 76.7%. Conclusion: The serum soluble PD-1 level is significantly increased in the death patients with pulmonary tuberculosis in ICU. Serum soluble PD-1 has certain clinical value in evaluating the severity and prognosis of tuberculosis patients admitted to the ICU.

Key words: Intensive care units, Tuberculosis, pulmonary, Programmed cell death 1 receptor, Prognosis

CLC Number:

R521

Wei Yunxia, Wang Xin, Lin Hongxia, Li Yishuai. Study on the correlation between serum soluble PD-1 and the severity and prognosis of pulmonary tuberculosis patients in ICU[J]. Journal of Tuberculosis and Lung Disease , 2025, 6(4): 426-431. doi: 10.19983/j.issn.2096-8493.20250032

Figures/Tables 4

指标	生存组(60例)	死亡组(42例)	统计检验值	P值
年龄[岁,M(Q₁,Q₃)]	63.00(58.00,70.25)	64.00(60.00,72.50)	Z=―0.885	0.376
性别[例,构成比(%)]			χ²=0.797	0.372
男性	44(73.33)	34(80.95)
女性	16(26.67)	8(19.05)
体质量指数(kg/m², $x ˉ$ ±s)	23.50±4.39	22.48±3.46	t=1.256	0.212
平均动脉压(mmHg, $x ˉ$ ±s)	85.63±13.60	80.38±13.34	t=1.933	0.056
心率[次/min,M(Q₁,Q₃)]	92.50(82.50,102.75)	96.50(89.00,111.75)	Z=―1.990	0.047

指标	生存组(60例)	死亡组(42例)	统计检验值	P值
氧合指数[mmHg,M(Q₁,Q₃)]	167.50(145.33,193.15)	147.90(118.15,176.44)	Z=―3.295	0.001
乳酸[mmol/L,M(Q₁,Q₃)]	1.30(0.90,1.78)	1.60(1.08,2.65)	Z=―1.696	0.090
白细胞计数[×10⁹/L,M(Q₁,Q₃)]	8.89(7.34,11.77)	10.26(6.35,14.91)	Z=1.176	0.239
前白蛋白[g/L,M(Q₁,Q₃)]	93.25(72.18,112.30)	76.85(59.13,133.20)	Z=―2.091	0.037
程序性死亡受体-1[pg/ml,M(Q₁,Q₃)]	35.45(28.40,41.80)	47.25(41.48,51.15)	Z=―6.399	<0.001
APACHEⅡ评分(分, $x ˉ$ ±s)	24.93±4.67	35.38±5.35	t=―10.479	<0.001
序贯器官衰竭评分[分,M(Q₁,Q₃)]	7.50(6.00,9.00)	12.00(10.75,14.00)	Z=―7.073	<0.001

指标	β值	s $x ˉ$ 值	Wald χ²值	OR值	95%CI值		P值
指标	β值	s $x ˉ$ 值	Wald χ²值	OR值	下限	上限	P值
心率	0.023	0.030	0.581	1.023	0.965	1.084	0.446
氧合指数	―0.021	0.016	1.746	0.979	0.949	1.010	0.186
前白蛋白	―0.018	0.012	2.145	0.982	0.958	1.006	0.143
程序性死亡受体-1	0.182	0.083	4.822	1.199	1.020	1.411	0.028
APACHEⅡ评分	0.303	0.133	5.209	1.354	1.044	1.757	0.022
序贯器官衰竭评分	0.510	0.223	5.236	1.666	1.076	2.579	0.022

References 40

[1]	Wang N, Meng F, Deng L, et al. The epidemiology and gene mutation characteristics of pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates in Southern China. Emerg Microbes Infect, 2025, 14(1): 2447607. doi:10.1080/22221751.2024.2447607.
[2]	张梦迪, 王琦琦, 王鑫, 等. 2005—2020年中国60岁及以上老年人群肺结核疾病负担研究. 中国防痨杂志, 2025, 47(3): 338-347. doi:10.19982/j.issn.1000-6621.20240508.
[3]	中华医学会结核病学分会重症专业委员会. 结核病重症加强治疗病房建设与管理专家共识(2018). 中华结核和呼吸杂志, 2018, 41(1): 19-24. doi:10.3760/cma.j.issn.1001-0939.2018.01.007.
[4]	Martyshkina YS, Tereshchenko VP, Bogdanova DA, et al. Reliable Hallmarks and Biomarkers of Senescent Lymphocytes. Int J Mol Sci, 2023, 24(21): 15653. doi:10.3390/ijms242115653.
[5]	Chen R, Zhou L. PD-1 signaling pathway in sepsis: Does it have a future. Clin Immunol, 2021, 229: 108742. doi:10.1016/j.clim.2021.108742.
[6]	喻晓雯, 张真奥, 谢建平. PD-1/PD-L1,PD-L2信号通路及其在宿主抗结核免疫中作用的研究进展. 中华结核和呼吸杂志, 2024, 47(5): 485-489. doi:10.3760/cma.j.cn112147-20230904-00133.
[7]	任坦坦, 詹森林, 王玉香, 等. PD-1/PD-L1抑制剂相关活动性结核病的临床特点及文献复习. 结核与肺部疾病杂志, 2023, 4(1): 27-32. doi:10.19983/j.issn.2096-8493.20220161.
[8]	中华人民共和国国家卫生和计划生育委员会. WS 288—2017 肺结核诊断. 结核与肺部疾病杂志, 2024, 5(4): 376-378. doi:10.19983/j.issn.2096-8493.2024022.
[9]	van der Poll T, van de Veerdonk FL, Scicluna BP, et al. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol, 2017, 17(7): 407-420. doi:10.1038/nri.2017.36. pmid: 28436424
[10]	Groeger S, Meyle J. The role of programmed death receptor (PD-)1/PD-ligand (L)1 in periodontitis and cancer. Periodontol 2000, 2024, 96(1): 150-169. doi:10.1111/prd.12548. pmid: 38351432
[11]	Shi X, Zhao H, Yu J, et al. Changes in PD-1 expression on T lymphocyte subsets and related immune indicators before and after definitive chemoradiotherapy for esophageal squamous cell carcinoma. Ann Med, 2025, 57(1): 2445190. doi:10.1080/07853890.2024.2445190.
[12]	Zhang S, Wang L, Li M, et al. The PD-1/PD-L pathway in rheumatic diseases. J Formos Med Assoc, 2021, 120(1 Pt 1): 48-59. doi:10.1016/j.jfma.2020.04.004.
[13]	朱晓玉, 李智伟, 贾金桐, 等. 急、慢性布鲁菌病患者外周血PD-1、LAG-3表达及相关细胞因子水平的变化. 检验医学, 2024, 39(12): 1173-1180. doi:10.3969/j.issn.1673-8640.2024.12.008.
[14]	姜建春, 姜新华, 周群英, 等. 结核性胸膜炎患者胸腔积液及血清PD-1/PD-L1通路蛋白表达及其诊断价值. 中华医院感染学杂志, 2021, 31(19): 2954-2958. doi:10.11816/cn.ni.2021-203284.
[15]	Bailly C, Thuru X, Quesnel B. Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases. Cancers (Basel), 2021, 13(12): 3034. doi:10.3390/cancers13123034.
[16]	Liu C, Jiang J, Gao L, et al. Soluble PD-1 aggravates progression of collagen-induced arthritis through Th1 and Th17 pathways. Arthritis Res Ther, 2015, 17: 340. doi:10.1186/s13075-015-0859-z. pmid: 26608464
[17]	Yamagiwa S, Ishikawa T, Waguri N, et al. Increase of Soluble Programmed Cell Death Ligand 1 in Patients with Chronic Hepatitis C. Int J Med Sci, 2017, 14(5): 403-411. doi:10.7150/ijms.18784. pmid: 28539815
[18]	Avendaño-Ortiz J, Rubio-Garrido M, Lozano-Rodríguez R, et al. Soluble PD-L1: a potential immune marker for HIV-1 infection and virological failure. Medicine (Baltimore), 2020, 99(20): e20065. doi:10.1097/MD.0000000000020065.
[19]	Beserra DR, Alberca RW, Branco ACCC, et al. Upregulation of PD-1 Expression and High sPD-L 1 Levels Associated with COVID-19 Severity. J Immunol Res, 2022, 2022: 9764002. doi:10.1155/2022/9764002.
[20]	Spec A, Shindo Y, Burnham CA, et al. T cells from patients with Candida sepsis display a suppressive immunophenotype. Crit Care, 2016, 20: 15. doi:10.1186/s13054-016-1182-z.
[21]	Coman O, Grigorescu BL, Huţanu A, et al. The Role of PD-1/PD-L1 and IL-7 in Lymphocyte Dynamics and Sepsis Progression: A Biomarker Study in Critically Ill Patients. Int J Mol Sci, 2024, 25(23): 12612. doi:10.3390/ijms252312612.
[22]	Zhang K, Xu Y, Li Z, et al. Elevated PD-1 and PDL-1 autoantibodies and association with tuberculosis. J Infect, 2025, 90(3): 106430. doi:10.1016/j.jinf.2025.106430.
[23]	杨舒琪, 李锋. 程序性死亡受体1/程序性死亡-配体1抑制剂在结核病研究中的进展. 结核与肺部疾病杂志, 2025, 6(1): 94-101. doi:10.19983/j.issn.2096-8493.2024141.
[24]	Barber DL, Sakai S, Kudchadkar RR, et al. Tuberculosis following PD-1 blockade for cancer immunotherapy. Sci Transl Med, 2019, 11(475): eaat2702. doi:10.1126/scitranslmed.aat2702.
[25]	Alvarez IB, Pasquinelli V, Jurado JO, et al. Role played by the programmed death-1-programmed death ligand pathway during innate immunity against Mycobacterium tuberculosis. J Infect Dis, 2010, 202(4): 524-532. doi:10.1086/654932. pmid: 20617899
[26]	McNab FW, Berry MP, Graham CM, et al. Programmed death ligand 1 is over-expressed by neutrophils in the blood of patients with active tuberculosis. Eur J Immunol, 2011, 41(7): 1941-1947. doi:10.1002/eji.201141421. pmid: 21509782
[27]	Hassan SS, Akram M, King EC, et al. PD-1, PD-L1 and PD-L 2 Gene Expression on T-Cells and Natural Killer Cells Declines in Conjunction with a Reduction in PD-1 Protein during the Intensive Phase of Tuberculosis Treatment. PLoS One, 2015, 10(9): e0137646. doi:10.1371/journal.pone.0137646.
[28]	Cao S, Li J, Lu J, et al. Mycobacterium tuberculosis antigens repress Th 1 immune response suppression and promotes lung cancer metastasis through PD-1/PDl-1 signaling pathway. Cell Death Dis, 2019, 10(2): 44. doi:10.1038/s41419-018-1237-y.
[29]	Stroh GR, Peikert T, Escalante P. Active and latent tuberculosis infections in patients treated with immune checkpoint inhibitors in a non-endemic tuberculosis area. Cancer Immunol Immunother, 2021, 70(11): 3105-3111. doi:10.1007/s00262-021-02905-8. pmid: 33770211
[30]	Shen L, Gao Y, Liu Y, et al. PD-1/PD-L pathway inhibits M.tb-specific CD4⁺ T-cell functions and phagocytosis of macrophages in active tuberculosis. Sci Rep, 2016, 6: 38362. doi:10.1038/srep38362. pmid: 27924827
[31]	Li K, Chen Y, Lin Y, et al. PD-1/PD-L 1 blockade is a potent adjuvant in treatment of Staphylococcus aureus osteomyelitis in mice. Mol Ther, 2023, 31(1): 174-192. doi:10.1016/j.ymthe.2022.09.006.
[32]	Kollu K, Akbudak Yerdelen E, Duran S, et al. Comparison of nutritional risk indices (PNI, GNRI, mNUTRIC) and HALP score in predicting adverse clinical outcomes in older patients staying in an intensive care unit. Medicine (Baltimore), 2024, 103(25): e38672. doi:10.1097/MD.0000000000038672.
[33]	孙静, 方堃, 任丹红, 等. 结核病危重患者的死亡预后因素初步分析. 中华结核和呼吸杂志, 2011, 34(1): 39-42. doi:10.3760/cma.j.issn.1001-0939.2011.01.013.
[34]	Marsh HM, Krishan I, Naessens JM, et al. Assessment of prediction of mortality by using the APACHE Ⅱ scoring system in intensive-care units. Mayo Clin Proc, 1990, 65(12): 1549-1557. doi:10.1016/s0025-6196(12)62188-0. pmid: 2123955
[35]	Zhang H, Tang X, Zhang J, et al. Serum prealbumin level as a biomarker of survival outcomes in patients with gastric cancer: a meta-analysis. Biomarkers, 2024, 29(6): 410-417. doi:10.1080/1354750X.2024.2402419. pmid: 39268816
[36]	Zhang HF, Li LQ, Ge YL, et al. Serum Prealbumin Improves the Sensitivity of Pneumonia Severity Index in Predicting 30-day Mortality of CAP Patients. Clin Lab, 2020, 66(5). doi:10.7754/Clin.Lab.2019.190929.
[37]	Yoshikawa M, Yoneda T, Maegawa J, et al. Relationship between nutritional depletion and cell-mediated immune function in active pulmonary tuberculosis. Kekkaku, 1994, 69(4): 307-316.
[38]	宋华峰, 吴妹英, 张建平, 等. 血清蛋白指标在构建肺结核治疗预后评估的早期预测模型中的应用价值. 中华结核和呼吸杂志, 2023, 46(7): 664-673. doi:10.3760/cma.j.cn112147-20221021-00836.
[39]	牛晓璇, 许雅鑫, 李宏宾, 等. 基于前白蛋白和T淋巴细胞计数的营养免疫评分与危重症患者预后的相关性. 中国临床医学, 2024, 31(6): 925-931. doi:10.12025/j.issn.1008-6358.2024.20241068.
[40]	Zhang Z, Liang Y, Zhong D, et al. Prognostic value of inflammation-immunity-nutrition score in patients with hepatocellular carcinoma treated with anti-PD-1 therapy. J Clin Lab Anal, 2022, 36(5): e24336. doi:10.1002/jcla.24336.