A transcriptomic atlas of chronic lung allograft dysfunction.

Summary

According to the abstract, high-resolution imaging-based gene expression profiling of 128 lung samples from explanted CLAD and donor lungs was analysed with weighted gene co-expression network analysis, and findings were validated across four datasets including a murine transplant model, human BOS lungs, transbronchial biopsies and bronchoalveolar lavage fluid. Unsupervised clustering revealed two transcriptomic CLAD endotypes aligning with mild-fibrotic (BOS, mild RAS) and advanced-fibrotic disease (moderate or severe RAS). Samples from the same patient often diverged molecularly. Five molecular programmes were described, from epithelial stress and innate immunity in early-fibrotic CLAD to progressive loss of homeostasis, and a 26-gene CLAD hub panel was reported to show robust diagnostic performance to discriminate CLAD. The authors conclude that BOS and RAS represent variable stages of a shared immunopathological continuum and that their findings support lung-specific molecular classifiers. Figures for diagnostic performance are not given in the indexed abstract. The PubMed affiliations name BREATHE, KU Leuven.

Details

doi

10.1183/13993003.02380-2025

pmid

42392829

authors

Beeckmans H, Kerckhof P, Geudens V, Vanluyten C, Zapata-Ortega M, Willems L, Van Herck A, Vermaut A, Aerts G, Hooft C, Jin X, Van Slambrouck J, Zajacova A, Mercurio M, Cortesi E, Mohamady Y, Tielemans B, Knoop C, Janssens W, Gayan-Ramirez G, Wuyts WA, Godinas L, Bos S, Wauters E, Dupont LJ, Van Raemdonck D, Weynand B, Saez-Gimenez B, Schiller HB, Schupp JC, Kneidinger N, De Sadeleer LJ, Ahangari F, McDonough JE, Ceulemans LJ, Yildirim AÖ, Kaminski N, Vanaudenaerde BM, Vos R

journal

European Respiratory Journal

year

2026

articleNumber

2502380

publishedOnline

2026-07-02

Sources and links

• Publisher record via DOI (primary)
• PubMed 42392829

Related

Links from this record

• related to: Molecular endotypes of CLAD (proposed framework)
• discusses: Bronchiolitis obliterans syndrome (BOS)
• discusses: Restrictive allograft syndrome (RAS)
• related to: Airway transcriptomic signatures
• affiliation named in PubMed record (BREATHE): KU Leuven BREATHE (Laboratory of Respiratory Diseases and Thoracic Surgery)

Linked from (derived)

• supports: Transbronchial biopsy: histology and transcript-based classifiers
• author: Bart Vanaudenaerde
• author: Robin Vos
• evidence: Clinical CLAD phenotypes are hard to assign reproducibly
• evidence: No validated molecular endotype scheme exists for CLAD

Known gaps in this record

• full text not read (abstract only)
• funding statement and grant numbers
• full author affiliations (only the PubMed affiliation text was checked for named centres)
• volume, issue and pages (only the article number and online date are listed by Crossref)
• diagnostic performance figures of the 26-gene panel (not in the indexed abstract)