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Published ahead of print on September 15, 2005, doi:10.1164/rccm.200504-644OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 2, January 2006, 188-198

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Submitted on April 25, 2005
Accepted on September 15, 2005

Gene Expression Profiles Distinguish Idiopathic Pulmonary Fibrosis from Hypersensitivity Pneumonitis

Moises Selman1, Annie Pardo2, Lourdes Barrera1, Andrea Estrada1, Susan R Watson3, Keith Wilson3, Natasha Aziz3, Naftali Kaminski4, and Albert Zlotnik3*

1 Instituto Nacional de Enfermedades Respiratorias, Tlalpan, Mexico DF, Mexico, 2 Universidad Nacional Autonoma de Mexico, Facultad de Ciencias,, Mexico DF, Mexico, 3 Eos Biotechnology, San Francisco, California, USA, 4 Department of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Simmons Center for Interstitial Lung Disease, Pittsburgh, Pennsylvania, USA

* To whom correspondence should be addressed. E-mail: azlotnik{at}neurocrine.com.

Rationale: Many of the interstitial lung diseases represent a diagnostic and therapeutic challenge since their clinical and even histological features are often non-specific. 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 non-specific interstitial pneumonia (NSIP) using custom oligonucleotide microarrays. Methods: We profiled lung biopsies from 15 patients with IPF, 12 with HP, and 8 with NSIP. Labeled complementary ribonucleic acid was hybridized to a custom Affymetrix oligonucleotide DNA microarray using standard Affymetrix protocols. The custom array, Hu03 contains 59,619 probesets 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 is enriched for genes that are functionally associated with inflammation, T cell activation and immune responses whereas the IPF signature is characterized by the expression of tissue remodeling, epithelial and myofibroblast genes. We then compared these gene expression signatures to classify NSIP, a histological pattern that is often difficult to differentiate consistently from HP and IPF. Two cases exhibited and IPF-like gene expression, another one could be more properly classified as HP, while 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.
Key words: microarrays, global transcription analysis, lung fibrosis, interstitial lung diseases, non-specific interstitial pneumonia




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