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[1]沙 敏,瞿秋霞,朱卫东,等.肺结核与肺结节病相关肉芽肿组织中CXCR5的差异性表达[J].中华肺部疾病杂志,2024,(02):189-194.[doi:10.3877/cma.j.issn.1674-6902.2024.02.004]
 Sha Min,Qu Qiuxia,Zhu Weidong,et al.Differential expression of CXCR5 molecule in pulmonary tuberculosis and pulmonary sarcoidosis-associated granulomatous tissues[J].,2024,(02):189-194.[doi:10.3877/cma.j.issn.1674-6902.2024.02.004]
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肺结核与肺结节病相关肉芽肿组织中CXCR5的差异性表达(PDF)

《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:
期数:
2024年02期
页码:
189-194
栏目:
论著
出版日期:
2024-04-25

文章信息/Info

Title:
Differential expression of CXCR5 molecule in pulmonary tuberculosis and pulmonary sarcoidosis-associated granulomatous tissues
作者:
沙 敏1瞿秋霞2朱卫东3陈 成1
215000 苏州,苏州大学附属第一医院呼吸与危重症医学科1、临床免疫学实验室2、病理科3
Author(s):
Sha Min1 Qu Qiuxia2 Zhu Weidong3 Chen Cheng1.
1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China; 2Laboratory of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215000, China; 3Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou 215000, China
关键词:
肺结节病 肺结核 肉芽肿性疾病 CXCR5 T细胞
Keywords:
Pulmonary sarcoidosis Pulmonary tuberculosis Granulomatous diseases CXCR5 T cells
分类号:
R563
DOI:
10.3877/cma.j.issn.1674-6902.2024.02.004
摘要:
目的 分析不同肺肉芽肿组织中CXCR5分子的表达差异及对肺结核与肺结节病的鉴别诊断意义。方法 选择2016年1月至2022年12月我院收治的经支气管镜下肺组织活检确诊为肺肉芽肿性炎患者43例,其中肺结节病15例、肺结核病28例; 应用免疫组织化学技术分析组织切片中CXCR5分子表达,采用双重免疫荧光标记法分析组织切片中CXCR5在CD8+ T细胞、CD4+ T细胞上的表达,进行定量评分。结果 肺结核肉芽肿组织中CXCR5阳性表达大于2分22例(78.57%),表达强度大于2分12例(42.86%),定量评分小于3分10例(35.71%)、定量评分大于6分8例(28.57%); 肺结节病肉芽肿组织中CXCR5阳性表达大于2分9例(60.00%),CXCR5表达强度小于2分15例(100.00%),定量评分小于3分11例(73.33%)。与肺结节病相比,肺结核肉芽肿组织中CXCR5分子表达强度升高,整体评分增加[(4.00±2.12)vs.(2.18±1.87)]分(P<0.05)。ROC分析表明,最佳cut-off值CXCR5表达定量评分为2.85分时,肺结核与肺结节病鉴别诊断AUC=0.733,特异性73.3%,敏感性64.3%。荧光共定位分析显示,和肺结节病相比,肺结核肉芽肿组织中滤泡CD4+ T细胞(0.7933 vs. 0.5150)和滤泡CD8+ T细胞的(0.8350 vs. 0.6100)浸润水平增加(P<0.05)。结论 肺结核与肺结节肉芽肿组织中CXCR5及表面标记的滤泡CD4+ T细胞和CD8+ T细胞的表达存在差异,具有鉴别诊断意义。
Abstract:
Objective To analyze CXCR5 molecule expression in different pulmonary granulomatous tissues and to explore its differential diagnostic value between pulmonary tuberculosis and pulmonary sarcoidosis. Methods 43 patients with lung granulomatosis were diagnosed by bronchoscopic lung tissue biopsy from the First Affiliated Hospital of Soochow University from January 2016 to December 2022. Fifteen cases of pulmonary sarcoidosis and 28 cases of pulmonary tuberculosis were comprehensively diagnosed. The expression of CXCR5 molecules in tissue sections was analyzed by immunohistochemistry. The expression of CXCR5 in CD8+ T cells and CD4+ T cells of granuloma tissue sections was analyzed by dual immunofluorescence labeling, and quantitative scoring was performed. Results In pulmonary tuberculosis granuloma tissues, there were 22 cases(78.57%)with positive expression of CXCR5 greater than 2 points, 12 cases(42.86%)with expression intensity greater than 2 points, 10 cases(35.71%)with quantitative scores less than 3 points, and 8 cases(28.57%)with quantitative scores greater than 6 points. In the granuloma tissues of pulmonary sarcoidosis, there were 9 cases(60.00%)with positive expression of CXCR5 greater than 2 points, and the intensity of CXCR5 expression was less than 2 points in 15 cases(100.00%), and 11 cases(73.33%)were less than 3 points. Compared with pulmonary sarcoidosis, the expression intensity of CXCR5 molecules in pulmonary tuberculous granulomatous tissues was increased. The overall score of CXCR5 molecular expression was also increased(4.00±2.12)vs.( 2.18±1.87)(P<0.05). According to the ROC analysis, CXCR5 expression quantitative score was the best cut-off value when it was equal to 2.85 points. The AUC of the differential diagnosis of pulmonary tuberculosis and pulmonary sarcoidosis was 0.733, with a specificity of 73.3% and a sensitivity of 64.3%. Fluorescence colocalization analysis showed that the infiltration levels of follicular CD4+ T cells(0.7933 vs. 0.5150)and follicular CD8+ T cells(0.8350 vs. 0.6100)in pulmonary tuberculosis granuloma tissues were also increased compared with pulmonary sarcoidosis(P<0.05). Conclusion There are differences in the expression of CXCR5 molecule and surface-labeled follicular CD4+ T cells and follicular CD8+ T cells in granulomatous tissues of pulmonary tuberculosis and pulmonary sarcoidosis, which has differential diagnostic value.

参考文献/References:

1 中国医师协会呼吸医师分会呼吸病理工作委员会及共识编写专家组. 肺肉芽肿性疾病病理诊断原则及流程专家建议[J]. 中华病理学杂志, 2021, 50(7): 719-727.
2 冯瑞娥. 做好肉芽肿性肺疾病的病理诊断及鉴别诊断[J]. 中华结核和呼吸杂志, 2020(12): 1004-1008.
3 路希维, 曾 谊, 王凌伟, 等. 结核病流行背景下胸内结节病与结核病临床鉴别与处置专家共识[J]. 中国防痨杂志, 2022, 44(12): 1227-1241.
4 Samantha R, Javier R, Radha G, et al. CXCR5+ T helper cells mediate protective immunity against tuberculosis[J]. J Clini Investiga, 2013, 123(2): 712-726.
5 Bold TD, Ernst JD. CD4+ T cell-dependent IFN-γ production by CD8+ effector T cells in Mycobacterium tuberculosis infection[J]. J Immunol, 2012, 189(5): 2530-2536.
6 中华医学会呼吸病学分会间质性肺疾病学组, 中国医师协会呼吸医师分会间质性肺疾病工作委员会. 中国肺结节病诊治专家共识[J]. 中华结核和呼吸杂志, 2019, 42(9): 685-693.
7 中华医学会, 中华医学会杂志社, 中华医学会全科医学分会, 等. 肺结核基层诊疗指南(2018年)[J]. 中华全科医师杂志, 2019, 18(8): 709-717.
8 Grunewald J, Spagnolo P, Wahlström J, et al. Immunogenetics of Disease-Causing Inflammation in Sarcoidosis[J]. Clin Rev All Immunol, 2015, 49(1): 19-35.
9 Mannes K, Thomas PS. Sarcoidosis: rarely a single system disorder[J]. Breathe, 2020, 16(4): 200207.
10 Agrawal R, Kee AR, Ang L, et al. Tuberculosis or sarcoidosis: Opposite ends of the same disease spectrum?[J]. Tuberculosis, 2016, 100(98): 21-26.
11 Guleria R, Mahashur A, Ghoshal AG, et al. Challenges in diagnosing Sarcoidosis in tuberculosis endemic regions: Clinical scenario in India[J]. Sarcoidosis Vasc Diffuse Lung Dis, 2016, 33(4): 381-384.
12 Mortaz E, Masjedi MR, Abedini A, et al. Common features of tuberculosis and sarcoidosis[J]. Int J Mycobacteriol, 2016, 1(5): S240-S241.
13 Thillai M, Atkins CP, Crawshaw A, et al. BTS Clinical Statement on pulmonary sarcoidosis[J]. Thorax, 2021, 76(1): 4-20.
14 Ma J, Yin H, Hao X, et al. Development of a random forest model to classify sarcoidosis and tuberculosis[J]. Am J Translat Res, 2021, 13(6): 6166-6174.
15 Jain R, Kumari R, Chakraborty S, et al. T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis[J]. Eur J Immunol, 2023, 53(10): e2250255.
16 Dong Y, Zhou L, Zhang C, et al. Detection of antigen Ag85B expression is useful for the diagnosis of tuberculosis, especially for those with an antituberculosis treatment history[J]. Am J Clin Pathol, 2023, 160(1): 62-71.
17 Purohit MR, Sviland L, Wiker H, et al. Rapid and specific diagnosis of extrapulmonary tuberculosis by immunostaining of tissues and aspirates with anti-MPT64[J]. Appl Immunohistochem Molecul Morphol, 2017, 25(4): 282-288.
18 Xue Z, Jia Y, Zhang J. Research progress on CXC chemokines and their receptors in tumor microenvironment[J]. Chin J Cancer Bioth, 2020: 715-724.
19 胡晓光, 陈灿灿, 张亚男, 等. 机体抗结核分枝杆菌感染的主要免疫细胞及其作用机制[J]. 结核与肺部疾病杂志, 2020, 1(1): 71-77.
20 Gustavsson M. New insights into the structure and function of chemokine receptor: chemokine complexes from an experimental perspective[J]. J Leukocyte Biol, 2020, 107(6): 1115-1122.
21 Torraca V, Tulotta C, Snaar-Jagalska BE, et al. The chemokine receptor CXCR4 promotes granuloma formation by sustaining a mycobacteria-induced angiogenesis programme[J]. Sci Reports, 2017, 7(1): 45061.
22 Dorhoi A, Kaufmann SHE. Pathology and immune reactivity: understanding multidimensionality in pulmonary tuberculosis[J]. Sem Immunopathol, 2016, 38: 153-166.
23 Zhou J, He X, Ou Y, et al. Role of CXCR5+ CD8+ T cells in human hepatitis B virus infection.[J]. Viral Hepat, 2023, 30(8): 638-645.
24 乔 敏, 李姗姗, 刘荣梅, 等. CC趋化因子和CXC趋化因子及其受体在结核分枝杆菌感染免疫应答中作用的研究进展[J]. 细胞与分子免疫学杂志, 2021, 37(4): 373-377.
25 Lewinsohn DM, Lewinsohn DA. The missing link in correlates of protective tuberculosis immunity: recognizing the infected cell[J]. Front Immunol, 2022, 13: 869057.
26 吴桂辉, 黄 涛, 罗 槑, 等. 活动性肺结核患者病情严重程度与维生素D及T细胞亚群的相关性分析[J/CD]. 中华肺部疾病杂志(电子版), 2020, 13(4): 510-512.
27 Ardain A, Domingo-Gonzalez R, Das S, et al. Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis[J]. Nature, 2019, 570(7762): 528-532.
28 Lu Y J, Barreira-Silva P, Boyce S, et al. CD4 T cell help prevents CD8 T cell exhaustion and promotes control of Mycobacterium tuberculosis infection[J]. Cell Reports, 2021, 36(11): 109696.
29 Chen ES, Moller DR. Etiologies of sarcoidosis[J]. Clin Rev All Immunol, 2015, 49: 6-18.
30 Cho HS, Kim SJ, Yoo JY. Sarcoidosis during treatment of pulmonary tuberculosis: a rare case report and review of the literature[J]. J Int Med Res, 2021, 49(4): 3000605211001632.
31 Gupta D, Agarwal R, Aggarwal AN, et al. Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis[J]. Eur Res J, 2007, 30(3): 508-516.
32 Yamaguchi T, Costabel U, McDowell A, et al. Immunohistochemical detection of potential microbial antigens in granulomas in the diagnosis of sarcoidosis[J]. J Clin Med, 2021, 10(5): 983.
33 Fang C, Huang H, Xu Z. Immunological evidence for the role of mycobacteria in sarcoidosis: a meta-analysis[J]. PLoS One, 2016, 11(8): e0154716.

备注/Memo

备注/Memo:
基金项目: 国家自然科学基金资助项目(81672280) 江苏省医学重点学科(ZDXK202201) 通信作者: 陈 成, Email: chencheng@suda.edu.cn
更新日期/Last Update: 2024-04-20