Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study
Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not...
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2021-06-01
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Online Access: | https://doi.org/10.1186/s12931-021-01779-9 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takafumi Niwamoto Tomohiro Handa Yuko Murase Yoshinari Nakatsuka Kiminobu Tanizawa Yoshio Taguchi Hiromi Tomioka Keisuke Tomii Hideo Kita Michihiro Uyama Michiko Tsuchiya Masahito Emura Tetsuji Kawamura Naoki Arai Machiko Arita Kazuko Uno Akihiko Yoshizawa Ryuji Uozumi Izumi Yamaguchi Fumihiko Matsuda Kazuo Chin Toyohiro Hirai |
spellingShingle |
Takafumi Niwamoto Tomohiro Handa Yuko Murase Yoshinari Nakatsuka Kiminobu Tanizawa Yoshio Taguchi Hiromi Tomioka Keisuke Tomii Hideo Kita Michihiro Uyama Michiko Tsuchiya Masahito Emura Tetsuji Kawamura Naoki Arai Machiko Arita Kazuko Uno Akihiko Yoshizawa Ryuji Uozumi Izumi Yamaguchi Fumihiko Matsuda Kazuo Chin Toyohiro Hirai Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study Respiratory Research CTACK Cutaneous T-cell-attracting chemokine CCL27 IPF Idiopathic pulmonary fibrosis Biomarker |
author_facet |
Takafumi Niwamoto Tomohiro Handa Yuko Murase Yoshinari Nakatsuka Kiminobu Tanizawa Yoshio Taguchi Hiromi Tomioka Keisuke Tomii Hideo Kita Michihiro Uyama Michiko Tsuchiya Masahito Emura Tetsuji Kawamura Naoki Arai Machiko Arita Kazuko Uno Akihiko Yoshizawa Ryuji Uozumi Izumi Yamaguchi Fumihiko Matsuda Kazuo Chin Toyohiro Hirai |
author_sort |
Takafumi Niwamoto |
title |
Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study |
title_short |
Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study |
title_full |
Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study |
title_fullStr |
Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study |
title_full_unstemmed |
Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study |
title_sort |
cutaneous t-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-993X |
publishDate |
2021-06-01 |
description |
Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not possible. This study aimed to evaluate serum cytokines/chemokines as potential biomarkers that can predict outcomes in IPF patients. Methods A multi-institutional prospective two-stage discovery and validation design using two independent cohorts was adopted. For the discovery analysis, serum samples from 100 IPF patients and 32 healthy controls were examined using an unbiased, multiplex immunoassay of 48 cytokines/chemokines. The serum cytokine/chemokine values were compared between IPF patients and controls; the association between multiplex measurements and survival time was evaluated in IPF patients. In the validation analysis, the cytokines/chemokines identified in the discovery analysis were examined in serum samples from another 81 IPF patients to verify the ability of these cytokines/chemokines to predict survival. Immunohistochemical assessment of IPF-derived lung samples was also performed to determine where this novel biomarker is expressed. Results In the discovery cohort, 18 cytokines/chemokines were significantly elevated in sera from IPF patients compared with those from controls. Interleukin-1 receptor alpha (IL-1Rα), interleukin-8 (IL-8), macrophage inflammatory protein 1 alpha (MIP-1α), and cutaneous T-cell-attracting chemokine (CTACK) were associated with survival: IL-1Rα, hazard ratio (HR) = 1.04 per 10 units, 95% confidence interval (95% CI) 1.01–1.07; IL-8, HR = 1.04, 95% CI 1.01–1.08; MIP-1α, HR = 1.19, 95% CI 1.00–1.36; and CTACK, HR = 1.12 per 100 units, 95% CI 1.02–1.21. A replication analysis was performed only for CTACK because others were previously reported to be potential biomarkers of interstitial lung diseases. In the validation cohort, CTACK was associated with survival: HR = 1.14 per 100 units, 95% CI 1.01–1.28. Immunohistochemistry revealed the expression of CTACK and CC chemokine receptor 10 (a ligand of CTACK) in airway and type II alveolar epithelial cells of IPF patients but not in those of controls. Conclusions CTACK is a novel prognostic biomarker of IPF. Trial registration None (because of no healthcare intervention) |
topic |
CTACK Cutaneous T-cell-attracting chemokine CCL27 IPF Idiopathic pulmonary fibrosis Biomarker |
url |
https://doi.org/10.1186/s12931-021-01779-9 |
work_keys_str_mv |
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doaj-272ec9eb56884ab48e37f489bee9a4532021-06-27T11:16:43ZengBMCRespiratory Research1465-993X2021-06-0122111110.1186/s12931-021-01779-9Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational studyTakafumi Niwamoto0Tomohiro Handa1Yuko Murase2Yoshinari Nakatsuka3Kiminobu Tanizawa4Yoshio Taguchi5Hiromi Tomioka6Keisuke Tomii7Hideo Kita8Michihiro Uyama9Michiko Tsuchiya10Masahito Emura11Tetsuji Kawamura12Naoki Arai13Machiko Arita14Kazuko Uno15Akihiko Yoshizawa16Ryuji Uozumi17Izumi Yamaguchi18Fumihiko Matsuda19Kazuo Chin20Toyohiro Hirai21Department of Respiratory Medicine, Kyoto University Graduate School of MedicineDepartment of Respiratory Medicine, Kyoto University Graduate School of MedicineDepartment of Respiratory Medicine, Kyoto University Graduate School of MedicineDepartment of Respiratory Care and Sleep Medicine, Kyoto University Graduate School of MedicineDepartment of Respiratory Medicine, Kyoto University Graduate School of MedicineDepartment of Respiratory Medicine, Tenri HospitalDepartment of Respiratory Medicine, Kobe City Medical Center West HospitalDepartment of Respiratory Medicine, Kobe City Medical Center General HospitalDepartment of Respiratory Medicine, Takatsuki Red Cross HospitalRespiratory Disease Center, Kitano Hospital, Tazuke Kofukai Medical, Research InstituteDepartment of Respiratory Medicine, Otowa HospitalDepartment of Respiratory Medicine, Kyoto City HospitalDepartment of Respiratory Medicine, Himeji Medical CenterNational Hospital Organization Ibaraki Higashi National HospitalDepartment of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central HospitalLouis Pasteur Center for Medical ResearchDepartment of Diagnostic Pathology, Kyoto University Graduate School of MedicineDepartment of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of MedicineCenter for Genomic Medicine, Kyoto University Graduate School of MedicineCenter for Genomic Medicine, Kyoto University Graduate School of MedicineDepartment of Respiratory Care and Sleep Medicine, Kyoto University Graduate School of MedicineDepartment of Respiratory Medicine, Kyoto University Graduate School of MedicineAbstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not possible. This study aimed to evaluate serum cytokines/chemokines as potential biomarkers that can predict outcomes in IPF patients. Methods A multi-institutional prospective two-stage discovery and validation design using two independent cohorts was adopted. For the discovery analysis, serum samples from 100 IPF patients and 32 healthy controls were examined using an unbiased, multiplex immunoassay of 48 cytokines/chemokines. The serum cytokine/chemokine values were compared between IPF patients and controls; the association between multiplex measurements and survival time was evaluated in IPF patients. In the validation analysis, the cytokines/chemokines identified in the discovery analysis were examined in serum samples from another 81 IPF patients to verify the ability of these cytokines/chemokines to predict survival. Immunohistochemical assessment of IPF-derived lung samples was also performed to determine where this novel biomarker is expressed. Results In the discovery cohort, 18 cytokines/chemokines were significantly elevated in sera from IPF patients compared with those from controls. Interleukin-1 receptor alpha (IL-1Rα), interleukin-8 (IL-8), macrophage inflammatory protein 1 alpha (MIP-1α), and cutaneous T-cell-attracting chemokine (CTACK) were associated with survival: IL-1Rα, hazard ratio (HR) = 1.04 per 10 units, 95% confidence interval (95% CI) 1.01–1.07; IL-8, HR = 1.04, 95% CI 1.01–1.08; MIP-1α, HR = 1.19, 95% CI 1.00–1.36; and CTACK, HR = 1.12 per 100 units, 95% CI 1.02–1.21. A replication analysis was performed only for CTACK because others were previously reported to be potential biomarkers of interstitial lung diseases. In the validation cohort, CTACK was associated with survival: HR = 1.14 per 100 units, 95% CI 1.01–1.28. Immunohistochemistry revealed the expression of CTACK and CC chemokine receptor 10 (a ligand of CTACK) in airway and type II alveolar epithelial cells of IPF patients but not in those of controls. Conclusions CTACK is a novel prognostic biomarker of IPF. Trial registration None (because of no healthcare intervention)https://doi.org/10.1186/s12931-021-01779-9CTACKCutaneous T-cell-attracting chemokineCCL27IPFIdiopathic pulmonary fibrosisBiomarker |