Chronic lung allograft dysfunction small airways reveal a lymphocytic inflammation gene signature.
Chronic lung allograft dysfunction small airways reveal a lymphocytic inflammation gene signature.
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慢性肺同种异体移植功能障碍小气道揭示了淋巴细胞炎症基因特征。
DOI：
10.1111/ajt.16293
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Greenland JR
中科院分区：
文献类型：
--
作者：
Dugger DT;Fung M;Hays SR;Singer JP;Kleinhenz ME;Leard LE;Golden JA;Shah RJ;Lee JS;Deiter F;Greenland NY;Jones KD;Langelier CR;Greenland JR
慢性同种异体肺移植功能障碍（Chronic lung allograft dysfunction， CLAD）是肺移植术后长期生存的主要障碍，需要新的机制生物标志物。淋巴细胞性支气管炎（LB）先于CLAD，具有明确的分子特征。我们假设这种LB分子特征与独立于感染的小气道刷牙中的CLAD有关。我们分别使用RNAseq和数字RNA计数对22例CLAD病例和27例匹配对照的小气道刷洗和经支气管活检的RNA表达进行了量化。采用Wilcoxon秩和检验比较覆层各层LB成因评分。我们在气道刷中进行了无偏倚的宿主转录组通路和微生物宏基因组分析，并比较了两种组织类型之间的机器学习分类器。CLAD气道刷的LB metagene评分升高（P = 0.002），对移植物失败的预测提高（P = 0.02）。基于气道刷的基因表达分类器优于使用经支气管活检的基因表达分类器。感染与微生物α -多样性降低相关（P≤0.04），但感染和α -多样性与LB基因表达均无相关性。综上所述，在该队列中，经支气管活检不明显的小气道基因表达变化与CLAD相关。气道刷毛分子分析诊断覆层肺炎值得在多中心队列中进一步研究。
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 = 0.002) and improved prediction of graft failure (P = 0.02). Gene expression classifiers based on airway brushes outperformed those using transbronchial biopsies. While infection was associated with decreased microbial alpha-diversity (P ≤0.04), 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.
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影响因子：
14.3
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1164/rccm.200706-951oc
发表时间：
2008-05-01
影响因子：
24.7
作者：
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影响因子：
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作者：
Gupta R;Kim S;Taylor MW
通讯作者：
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DOI：
10.1056/nejmoa1504601
发表时间：
2015-07-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
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