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Chronic lung allograft dysfunction small airways reveal a lymphocytic inflammation gene signature
Author(s) -
Dugger Daniel T.,
Fung Monica,
Hays Steven R.,
Singer Jonathan P.,
Kleinhenz Mary E.,
Leard Lorriana E.,
Golden Jeffrey A.,
Shah Rupal J.,
Lee Joyce S.,
Deiter Fred,
Greenland Nancy Y.,
Jones Kirk D.,
Langelier Chaz R.,
Greenland John R.
Publication year - 2021
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.16293
Subject(s) - medicine , gene signature , transcriptome , lung transplantation , airway , lung , gene expression , pathology , gene , immunology , biology , surgery , biochemistry
Chronic lung allograft dysfunction (CLAD) is the major barrier to long‐term survival following lung transplantation, and new mechanistic biomarkers are needed. Lymphocytic bronchitis (LB) precedes CLAD and has a defined molecular signature. We hypothesized that this LB molecular signature would be associated with CLAD in small airway brushings independent of infection. We quantified RNA expression from small airway brushings and transbronchial biopsies, using RNAseq and digital RNA counting, respectively, for 22 CLAD cases and 27 matched controls. LB metagene scores were compared across CLAD strata by Wilcoxon rank sum test. We performed unbiased host transcriptome pathway and microbial metagenome analysis in airway brushes and compared machine‐learning classifiers between the two tissue types. This LB metagene score was increased in CLAD airway brushes ( p = .002) and improved prediction of graft failure ( p = .02). Gene expression classifiers based on airway brushes outperformed those using transbronchial biopsies. While infection was associated with decreased microbial alpha‐diversity ( p ≤ .04), neither infection nor alpha‐diversity was associated with LB gene expression. In summary, CLAD was associated with small airway gene expression changes not apparent in transbronchial biopsies in this cohort. Molecular analysis of airway brushings for diagnosing CLAD merits further examination in multicenter cohorts.