Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis
Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis
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DOI：
10.1164/rccm.200504-644oc
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发表时间：
2006-01-15
影响因子：
24.7
通讯作者：
Zlotnik, A
中科院分区：
文献类型：
--
作者：
Selman, M;Pardo, A;Zlotnik, A
基本原理：许多间质性肺疾病的诊断和治疗的挑战，因为他们的临床，甚至组织学特征往往是非特异性的。同样，他们中的大多数人的转录签名是unknown.Objective：To comparison the gene expression patterns from patients with idiopathic pulmonary fibrosis（IPF），hypersensitivity pneumonitis（HP），and nonspecific interstitial pneumonia（NSIP）using custom oligonucleotide microarrays.Methods：We profiled lung biopsy from 15 patients with IPF，12 with HP，and 8 with NSIP.使用标准的Affytron方案将标记的互补核糖核酸与定制的Affytron寡核苷酸DNA微阵列杂交。自定义阵列Hu03包含59，619个探针组，代表估计的46，000个基因clusters.Results：我们鉴定了统计学上显著的HP和IPF基因表达特征。HP基因表达特征富集了与炎症、T细胞活化和免疫应答功能相关的基因，而IPF特征的特征在于组织重塑、上皮和肌成纤维细胞基因的表达。然后，我们比较了这些基因表达特征，对NSIP进行分类，NSIP是一种通常难以与HP和IPF一致区分的组织学模式。两例表现出IPF样基因表达，另一个可以更恰当地分类为HP，而其他人并不像HP或IPF，这表明他们可能代表特发性NSIP.Conclusions：我们的研究结果强调的价值基因表达签名分类间质性肺疾病和了解致病机制，并提出新的方法来提高诊断和治疗这些疾病的患者。
Rationale: Many of the interstitial lung diseases represent a diagnostic and therapeutic challenge because their clinical and even histologic features are often nonspecific. Likewise, the transcriptional signatures of most of them are unknown.Objective: To compare the gene expression patterns from patients with idiopathic pulmonary fibrosis (IPF) hypersensitivity pneumonitis (HP), and nonspecific interstitial pneumonia (NSIP) using custom oligonucleotide microarrays.Methods: We profiled lung biopsies from 15 patients with IPF, 12 with HP, and eight with NSIP. Labeled complementary ribonucleic acid was hybridized to a custom Affymetrix oligonucleotide DNA microarray using standard Affymetrix protocols. The custom array, Hu03, contained 59,619 probe sets representing an estimated 46,000 gene clusters.Results: We identified statistically significant gene expression signatures that characterize HP and IPF. The HP gene expression signature was enriched for genes that are functionally associated with inflammation, T-cell activation, and immune responses, whereas the IPF signature was characterized by the expression of tissue remodeling, epithelial, and myofibroblast genes. We then compared these gene expression signatures to classify NSIP, a histologic pattern that is often difficult to differentiate consistently from HP and IPF. Two cases exhibited an IPF-like gene expression, another one could be more properly classified as HP, whereas others did not resemble HP or IPF, suggesting that they may represent idiopathic NSIP.Conclusions: Our results underscore the value of gene expression signatures to classify the interstitial lung diseases and to understand pathogenic mechanisms, and suggest new ways to improve the diagnosis and treatment of patients with these diseases.