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Published in: Respiratory Research 1/2022

01-12-2022 | Cytokines | Research

Immunophenotype in acute exacerbation of chronic obstructive pulmonary disease: a cross-sectional study

Authors: Xiao-feng Xiong, Min Zhu, Hong-xia Wu, Li-li Fan, De-yun Cheng

Published in: Respiratory Research | Issue 1/2022

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Abstract

Background

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, and the immune inflammatory response is thought to play an important role in pathogenesis. However, the immunophenotype of patients with COPD is unknown. Herein, we evaluated the immunophenotype of patients with acute exacerbation of COPD (AECOPD).

Methods

A cross-sectional study was conducted in West China Hospital from September 2018 to October 2019. The proportion of CD4 + T lymphocyte subtypes (Th1, Th2, Th17 and Treg) and levels of serum cytokines in the peripheral blood of patients with AECOPD, stable COPD (SCOPD), healthy smokers (HSs)and healthy controls (HCs) were evaluated.

Results

A total of 15 HCs, 19 HSs, 42 patients with SCOPD, and 55 patients with AECOPD were included. Compared to patients with SCOPD, Th1 cells, Th17 cells, Treg cell ratio, Th1/Th2 cell ratio, and the levels of C-reactive protein, interleukin (IL)-6, and IL-10 were significantly increased in patients with AECOPD (P < 0.001), while the proportion of Th2 cells was significantly reduced (P < 0.01). The proportion of Th17 cells was positively correlated with COPD Assessment Test score (r = 0.266, P = 0.009), modified Medical Research Council dyspnea score (r = 0.858, P < 0.0001), and Th1 cell ratio (r = 0.403, P < 0.0001) and negatively correlated with forced vital capacity (r = − 0.367, P = 0.009) and proportion of Th2 cells (r = − 0.655, P < 0.0001).

Conclusions

The immunophenotype of patients with AECOPD shows abnormal activation of Th1, Th17, and Treg cells. There is a correlation between the proportion of Th17 cells and the severity of COPD; therefore, this may represent a novel index for the evaluation of COPD severity.
Trial registration: China Clinical Trials Registry, ChiCTR1800018452, registered 19 September 2018, https://​www.​chictr.​org.​cn/​index.​aspx.
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Literature
2.
go back to reference Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, Fabbri LM, Goldin JG, Jones PW, Macnee W, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med. 2010;182:598–604.CrossRef Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, Fabbri LM, Goldin JG, Jones PW, Macnee W, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med. 2010;182:598–604.CrossRef
3.
go back to reference Siafakas N, Corlateanu A, Fouka E. Phenotyping before starting treatment in COPD? COPD. 2017;14:367–74.CrossRef Siafakas N, Corlateanu A, Fouka E. Phenotyping before starting treatment in COPD? COPD. 2017;14:367–74.CrossRef
4.
go back to reference Pinto LM, Alghamdi M, Benedetti A, Zaihra T, Landry T, Bourbeau J. Derivation and validation of clinical phenotypes for COPD: a systematic review. Respir Res. 2015;16:50.CrossRef Pinto LM, Alghamdi M, Benedetti A, Zaihra T, Landry T, Bourbeau J. Derivation and validation of clinical phenotypes for COPD: a systematic review. Respir Res. 2015;16:50.CrossRef
5.
go back to reference Chen Y, Zhan X, Zhang M. Study on the proportion of Th17 and Treg cells and the level of inflammatory factors in elderly patients with COPD at different stages. J Clin Exp Med. 2015;20:83–6. Chen Y, Zhan X, Zhang M. Study on the proportion of Th17 and Treg cells and the level of inflammatory factors in elderly patients with COPD at different stages. J Clin Exp Med. 2015;20:83–6.
6.
go back to reference Zheng X, Zhang L, Chen J, Gu Y, Xu J, Ouyang Y. Dendritic cells and Th17/Treg ratio play critical roles in pathogenic process of chronic obstructive pulmonary disease. Biomed Pharmacother. 2018;108:1141–51.CrossRef Zheng X, Zhang L, Chen J, Gu Y, Xu J, Ouyang Y. Dendritic cells and Th17/Treg ratio play critical roles in pathogenic process of chronic obstructive pulmonary disease. Biomed Pharmacother. 2018;108:1141–51.CrossRef
7.
go back to reference Wang H, Ying H, Wang S, Gu X, Weng Y, Peng W, Xia D, Yu W. Imbalance of peripheral blood Th17 and Treg responses in patients with chronic obstructive pulmonary disease. Clin Respir J. 2015;9:330–41.CrossRef Wang H, Ying H, Wang S, Gu X, Weng Y, Peng W, Xia D, Yu W. Imbalance of peripheral blood Th17 and Treg responses in patients with chronic obstructive pulmonary disease. Clin Respir J. 2015;9:330–41.CrossRef
8.
go back to reference Domagala-Kulawik J, Hoser G, Dabrowska M, Safianowska A, Chazan R. CD4+/CD25+ cells in systemic inflammation in COPD. Scand J Immunol. 2011;73:59–65.CrossRef Domagala-Kulawik J, Hoser G, Dabrowska M, Safianowska A, Chazan R. CD4+/CD25+ cells in systemic inflammation in COPD. Scand J Immunol. 2011;73:59–65.CrossRef
9.
go back to reference Ghany MF, Makhlouf HA, Gaber N. Downregulation of regulatory T cells in patients with chronic obstructive pulmonary disease: relation to disease severity. Egypt J Chest Dis Tuberc. 2018;67:351. Ghany MF, Makhlouf HA, Gaber N. Downregulation of regulatory T cells in patients with chronic obstructive pulmonary disease: relation to disease severity. Egypt J Chest Dis Tuberc. 2018;67:351.
10.
go back to reference Chiappori A, Folli C, Balbi F, Caci E, Riccio AM, De Ferrari L, Melioli G, Braido F, Canonica GW. CD4(+)CD25(high)CD127(-) regulatory T-cells in COPD: smoke and drugs effect. World Allergy Organ J. 2016;9:5.CrossRef Chiappori A, Folli C, Balbi F, Caci E, Riccio AM, De Ferrari L, Melioli G, Braido F, Canonica GW. CD4(+)CD25(high)CD127(-) regulatory T-cells in COPD: smoke and drugs effect. World Allergy Organ J. 2016;9:5.CrossRef
12.
go back to reference Zhang Y, Yan Q, Liu H. Expression of Treg in peripheral blood and lung tissue of patients with chronic obstructive pulmonary disease. Acta Univ Med Anhui. 2015;50:679–82. Zhang Y, Yan Q, Liu H. Expression of Treg in peripheral blood and lung tissue of patients with chronic obstructive pulmonary disease. Acta Univ Med Anhui. 2015;50:679–82.
13.
go back to reference Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity. 2008;28:454–67.CrossRef Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity. 2008;28:454–67.CrossRef
14.
go back to reference Zhang L, Cheng Z, Liu W, Wu K. Expression of interleukin (IL)-10, IL-17A and IL-22 in serum and sputum of stable chronic obstructive pulmonary disease patients. COPD. 2013;10:459–65.CrossRef Zhang L, Cheng Z, Liu W, Wu K. Expression of interleukin (IL)-10, IL-17A and IL-22 in serum and sputum of stable chronic obstructive pulmonary disease patients. COPD. 2013;10:459–65.CrossRef
15.
go back to reference Di Stefano A, Caramori G, Gnemmi I, Contoli M, Vicari C, Capelli A, Magno F, D’Anna SE, Zanini A, Brun P, et al. T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients. Clin Exp Immunol. 2009;157:316–24.CrossRef Di Stefano A, Caramori G, Gnemmi I, Contoli M, Vicari C, Capelli A, Magno F, D’Anna SE, Zanini A, Brun P, et al. T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients. Clin Exp Immunol. 2009;157:316–24.CrossRef
16.
go back to reference Vargas-Rojas MI, Ramirez-Venegas A, Limon-Camacho L, Ochoa L, Hernandez-Zenteno R, Sansores RH. Increase of Th17 cells in peripheral blood of patients with chronic obstructive pulmonary disease. Respir Med. 2011;105:1648–54.CrossRef Vargas-Rojas MI, Ramirez-Venegas A, Limon-Camacho L, Ochoa L, Hernandez-Zenteno R, Sansores RH. Increase of Th17 cells in peripheral blood of patients with chronic obstructive pulmonary disease. Respir Med. 2011;105:1648–54.CrossRef
17.
go back to reference The global initiative for chronic obstructive lung disease. GOLD 2017 global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease 2017 report [EB/OL]. (2016–11–16) [2017–01–03]. http://www.goldcopd.org. The global initiative for chronic obstructive lung disease. GOLD 2017 global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease 2017 report [EB/OL]. (2016–11–16) [2017–01–03]. http://​www.​goldcopd.​org.
18.
go back to reference Huang WC, Wu MF, Chen HC, Hsu JY, Group T. Features of COPD patients by comparing CAT with mMRC: a retrospective, cross-sectional study. NPJ Prim Care Respir Med. 2015;25:15063.CrossRef Huang WC, Wu MF, Chen HC, Hsu JY, Group T. Features of COPD patients by comparing CAT with mMRC: a retrospective, cross-sectional study. NPJ Prim Care Respir Med. 2015;25:15063.CrossRef
20.
go back to reference Ruhle PF, Fietkau R, Gaipl US, Frey B. Development of a modular assay for detailed immunophenotyping of peripheral human whole blood samples by multicolor flow cytometry. Int J Mol Sci. 2016; 17. Ruhle PF, Fietkau R, Gaipl US, Frey B. Development of a modular assay for detailed immunophenotyping of peripheral human whole blood samples by multicolor flow cytometry. Int J Mol Sci. 2016; 17.
21.
go back to reference Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol. 2007;8:639–46.CrossRef Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol. 2007;8:639–46.CrossRef
22.
go back to reference Nguyen QP, Deng TZ, Witherden DA, Goldrath AW. Origins of CD4(+) circulating and tissue-resident memory T-cells. Immunology. 2019;157:3–12.CrossRef Nguyen QP, Deng TZ, Witherden DA, Goldrath AW. Origins of CD4(+) circulating and tissue-resident memory T-cells. Immunology. 2019;157:3–12.CrossRef
23.
go back to reference Sun J, Liu T, Yan Y, Huo K, Zhang W, Liu H, Shi Z. The role of Th1/Th2 cytokines played in regulation of specific CD4 (+) Th1 cell conversion and activation during inflammatory reaction of chronic obstructive pulmonary disease. Scand J Immunol. 2018;88: e12674.CrossRef Sun J, Liu T, Yan Y, Huo K, Zhang W, Liu H, Shi Z. The role of Th1/Th2 cytokines played in regulation of specific CD4 (+) Th1 cell conversion and activation during inflammatory reaction of chronic obstructive pulmonary disease. Scand J Immunol. 2018;88: e12674.CrossRef
24.
go back to reference Amedei A, Della Bella C, Niccolai E, Stanflin N, Benagiano M, Duranti R, Del Prete G, Murphy TF, D’Elios MM. Moraxella catarrhalis-specific Th1 cells in BAL fluids of chronic obstructive pulmonary disease patients. Int J Immunopathol Pharmacol. 2009;22:979–90.CrossRef Amedei A, Della Bella C, Niccolai E, Stanflin N, Benagiano M, Duranti R, Del Prete G, Murphy TF, D’Elios MM. Moraxella catarrhalis-specific Th1 cells in BAL fluids of chronic obstructive pulmonary disease patients. Int J Immunopathol Pharmacol. 2009;22:979–90.CrossRef
25.
go back to reference Arellano G, Acuna E, Reyes LI, Ottum PA, De Sarno P, Villarroel L, Ciampi E, Uribe-San Martin R, Carcamo C, Naves R. Th1 and Th17 cells and associated cytokines discriminate among clinically isolated syndrome and multiple sclerosis phenotypes. Front Immunol. 2017;8:753.CrossRef Arellano G, Acuna E, Reyes LI, Ottum PA, De Sarno P, Villarroel L, Ciampi E, Uribe-San Martin R, Carcamo C, Naves R. Th1 and Th17 cells and associated cytokines discriminate among clinically isolated syndrome and multiple sclerosis phenotypes. Front Immunol. 2017;8:753.CrossRef
26.
go back to reference Bruchard M, Rebe C, Derangere V, Togbe D, Ryffel B, Boidot R, Humblin E, Hamman A, Chalmin F, Berger H, et al. The receptor NLRP3 is a transcriptional regulator of TH2 differentiation. Nat Immunol. 2015;16:859–70.CrossRef Bruchard M, Rebe C, Derangere V, Togbe D, Ryffel B, Boidot R, Humblin E, Hamman A, Chalmin F, Berger H, et al. The receptor NLRP3 is a transcriptional regulator of TH2 differentiation. Nat Immunol. 2015;16:859–70.CrossRef
27.
go back to reference Wei B, Sheng Li C. Changes in Th1/Th2-producing cytokines during acute exacerbation chronic obstructive pulmonary disease. J Int Med Res. 2018;46:3890–902.CrossRef Wei B, Sheng Li C. Changes in Th1/Th2-producing cytokines during acute exacerbation chronic obstructive pulmonary disease. J Int Med Res. 2018;46:3890–902.CrossRef
28.
go back to reference Hirai K, Shirai T, Suzuki M, Akamatsu T, Suzuki T, Hayashi I, Yamamoto A, Akita T, Morita S, Asada K, et al. A clustering approach to identify and characterize the asthma and chronic obstructive pulmonary disease overlap phenotype. Clin Exp Allergy. 2017;47:1374–82.CrossRef Hirai K, Shirai T, Suzuki M, Akamatsu T, Suzuki T, Hayashi I, Yamamoto A, Akita T, Morita S, Asada K, et al. A clustering approach to identify and characterize the asthma and chronic obstructive pulmonary disease overlap phenotype. Clin Exp Allergy. 2017;47:1374–82.CrossRef
29.
go back to reference Yang L, Ou Y. Study on the role of DCs, Th1 and Th2 cells in the immune mechanism of COPD. J Med Recapitul. 2018;24:4427–32. Yang L, Ou Y. Study on the role of DCs, Th1 and Th2 cells in the immune mechanism of COPD. J Med Recapitul. 2018;24:4427–32.
30.
go back to reference Jin Y, Wan Y, Chen G, Chen L, Zhang MQ, Deng L, Zhang JC, Xiong XZ, Xin JB. Treg/IL-17 ratio and Treg differentiation in patients with COPD. PLoS ONE. 2014;9: e111044.CrossRef Jin Y, Wan Y, Chen G, Chen L, Zhang MQ, Deng L, Zhang JC, Xiong XZ, Xin JB. Treg/IL-17 ratio and Treg differentiation in patients with COPD. PLoS ONE. 2014;9: e111044.CrossRef
31.
go back to reference Shan M, Cheng HF, Song LZ, Roberts L, Green L, Hacken-Bitar J, Huh J, Bakaeen F, Coxson HO, Storness-Bliss C, et al. Lung myeloid dendritic cells coordinately induce TH1 and TH17 responses in human emphysema. Sci Transl Med. 2009;1:4ra10.CrossRef Shan M, Cheng HF, Song LZ, Roberts L, Green L, Hacken-Bitar J, Huh J, Bakaeen F, Coxson HO, Storness-Bliss C, et al. Lung myeloid dendritic cells coordinately induce TH1 and TH17 responses in human emphysema. Sci Transl Med. 2009;1:4ra10.CrossRef
32.
go back to reference Yang X, Huo B, Zhong X, Su W, Liu W, Li Y, He Z, Bai J. Imbalance between subpopulations of regulatory T cells in patients with acute exacerbation of COPD. COPD. 2017;14:618–25.CrossRef Yang X, Huo B, Zhong X, Su W, Liu W, Li Y, He Z, Bai J. Imbalance between subpopulations of regulatory T cells in patients with acute exacerbation of COPD. COPD. 2017;14:618–25.CrossRef
Metadata
Title
Immunophenotype in acute exacerbation of chronic obstructive pulmonary disease: a cross-sectional study
Authors
Xiao-feng Xiong
Min Zhu
Hong-xia Wu
Li-li Fan
De-yun Cheng
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2022
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-022-02058-x

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