Evidence map›Paper›PMID 40269953›Full record

ArticleRespiratory research2025

Serum C-C motif chemokine ligand 17 as a predictive biomarker for the progression of non-idiopathic pulmonary fibrosis interstitial lung disease.

Takatoshi Enomoto, Yoshito Takeda, Yuya Shirai, Takehiro Hasegawa, Feng Zhao, Hanna Lunding, Moritz Pohl, Ryuya Edahiro, Shigeyuki Shichino, Takahiro Kawasaki and 26 more

Abstract read
In one paragraph

Article in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors.

Takatoshi EnomotoDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yoshito TakedaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. yoshito@imed3.med.osaka-u.ac.jp.
Yuya ShiraiDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takehiro HasegawaResearch and Development Division, Sysmex R&D Center Europe GmbH, Hamburg, Germany.
Feng ZhaoResearch and Development Division, Sysmex R&D Center Europe GmbH, Hamburg, Germany.
Hanna LundingResearch and Development Division, Sysmex R&D Center Europe GmbH, Hamburg, Germany.
Moritz PohlResearch and Development Division, Sysmex R&D Centre UK, Cambridge, UK.
Ryuya EdahiroDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Shigeyuki ShichinoDivision of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
Takahiro KawasakiDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Hanako YoshimuraDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Reina HaraDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Saori AmiyaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Makoto YamamotoDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Daisuke NakatsuboDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Satoshi TanizakiDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Mana NakayamaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yoshimi NodaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takayuki NiitsuDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yuichi AdachiDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Mari ToneDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yuko AbeDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Maiko NaitoDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kentaro MasuhiroDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yujiro NaitoDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takayuki ShiroyamaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kotaro MiyakeDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Shohei KoyamaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kiyoharu FukushimaDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kota IwahoriDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Haruhiko HirataDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Izumi NagatomoDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Satoshi NojimaDepartment of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Masahiro YanagawaDepartment of Radiology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yoshikazu InoueClinical Research Center, NHO Kinki Chuo Chest Medical Center, Sakai, Osaka, Japan.
Atsushi KumanogohDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Funding

Japan Agency for Medical Research and Development JP21gm6210025Japan Agency for Medical Research and Development JP223fa627002Japan Society for the Promotion of Science Grant-in-Aid for Transformative Research Areas (B) 22H05064Japan Society for the Promotion of Science JP18H05282Japan Society for the Promotion of Science JP19K08650
6 · The paper itself

Abstract

backgroundInterstitial lung disease (ILD), represented by idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), shows poor prognosis due to progressive fibrosis. Early therapeutic intervention is required to enhance the efficacy of antifibrotic drugs, highlighting the importance of early detection of ILD progression. Although candidate biomarkers for predicting ILD progression have been recently reported through omics analyses, clinically measurable biomarkers remain unestablished. This study aimed to identify clinically measurable biomarkers that could predict the degree of ILD progression.

methodsThe serum levels of 13 candidate biomarkers were prospectively measured by chemiluminescent enzyme immunoassay and the utilities for predicting ILD progression were compared in the discovery cohort (total 252 patients). Moreover, we evaluated the utility of the identified biomarker in another independent cohort (154 patients with non-IPF-ILD) and examined the dynamics of the biomarker by immunoblotting and single-cell RNA sequencing (scRNA-seq) using samples of patients and a mouse model.

resultsIn the discovery cohort, C-C motif chemokine ligand (CCL)17 could reliably predict ILD progression, particularly in patients with ILD other than IPF, and showed significant associations with mortality (hazard ratio [HR] 3.70; 95% confidence interval [CI] 1.19-11.49; P = 0.015; cut-off value = 418 pg/mL). Consistently, in the validation cohort, the CCL17 high group showed significantly higher mortality (HR: 2.15; 95% CI 0.99-4.69; P = 0.049), and CCL17 was identified as an independent prognostic factor from corticosteroid or immunosuppressive agents use and ILD-gender-age-physiology index. Similar to the results of serum studies, CCL17 levels in the lungs of patients with PPF and model mice were higher than those in controls. They were positively correlated with CCL17 levels in the serum, suggesting that the increased serum CCL17 levels could reflect an increase in CCL17 levels in lung tissues. The scRNA-seq analysis of lung tissues from model mice suggested that the levels of CCL17 derived primarily from conventional dendritic cells and macrophages increased, especially during the profibrotic phase.

conclusionsWe identified serum CCL17 as a clinically measurable biomarker for predicting non-IPF-ILD progression. Serum CCL17 could enable the stratification of patients at risk of non-IPF-ILD progression, leading to appropriate early therapeutic intervention.

Indexed as

Chemokine CCL17Disease ProgressionLung Diseases, InterstitialAgedAnimalsBiomarkersCohort StudiesFemaleHumansIdiopathic Pulmonary FibrosisMaleMiceMice, Inbred C57BLMiddle AgedPredictive Value of TestsPrognosisBiomarkersCCL17 protein, humanChemokine CCL17FibrosisInterstitialLung diseasesPeriostinPrognosisPulmonary surfactant-associated protein B

Identifiers

PMID40269953
PMCPMC12020124

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.