Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis.

Abstract

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.

• Authors: Moises Selman, Annie Pardo, Lourdes Barrera, Andrea Estrada, Susan R Watson, Keith Wilson, Natasha Aziz, Naftali Kaminski, Albert Zlotnik
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 173 Issue 2 Pg. 188-98 (Jan 15 2006) ISSN: 1073-449X [Print] United States
• PMID: 16166619 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Alveolitis, Extrinsic Allergic (diagnosis, genetics)
• Biopsy (methods)
• Diagnosis, Differential
• Female
• Gene Expression (genetics, physiology)
• Gene Expression Profiling (methods)
• Humans
• Immunity (genetics)
• Inflammation (genetics)
• Lung (surgery)
• Male
• Middle Aged
• Oligonucleotide Array Sequence Analysis (methods)
• Pulmonary Fibrosis (diagnosis, genetics)
• T-Lymphocytes (physiology)