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Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study
- Source :
- Respiratory Research, Respiratory Research, Vol 22, Iss 1, Pp 1-11 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
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)
- Subjects :
- Male
0301 basic medicine
Oncology
Chemokine
CC chemokine receptor 10
medicine.medical_treatment
Idiopathic pulmonary fibrosis
0302 clinical medicine
Medicine
Prospective Studies
Macrophage inflammatory protein
Multiplex
biology
CTACK
respiratory system
Middle Aged
Prognosis
Cytokine
medicine.anatomical_structure
Disease Progression
Biomarker (medicine)
Female
Adult
medicine.medical_specialty
Diseases of the respiratory system
03 medical and health sciences
Internal medicine
Humans
Aged
Lung
RC705-779
business.industry
Chemokine CCL27
Research
Biomarker
medicine.disease
Cutaneous T-cell-attracting chemokine
respiratory tract diseases
IPF
030104 developmental biology
030228 respiratory system
CCL27
biology.protein
business
CC chemokine receptors
Biomarkers
Subjects
Details
- ISSN :
- 1465993X
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Respiratory Research
- Accession number :
- edsair.doi.dedup.....66c472e91a82209cb745f09a241f8acf