Gene Expression Profiles Distinguish Idiopathic Pulmonary Fibrosis from Hypersensitivity Pneumonitis

• Published in: American journal of respiratory and critical care medicine Vol. 173; no. 2; pp. 188 - 198
• Main Authors: Selman, Moises, Pardo, Annie, Barrera, Lourdes, Estrada, Andrea, Watson, Susan R, Wilson, Keith, Aziz, Natasha, Kaminski, Naftali, Zlotnik, Albert
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.01.2006; American Lung Association; American Thoracic Society
• Subjects: Alveolitis, Extrinsic Allergic - diagnosis; Alveolitis, Extrinsic Allergic - genetics; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Biopsy - methods; Blood and lymphatic vessels; C. Interstitial Lung Disease; Cardiology. Vascular system; Diagnosis, Differential; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Gene Expression - genetics; Gene Expression - physiology; Gene Expression Profiling - methods; Humans; Immunity - genetics; Inflammation - genetics; Intensive care medicine; Lung - surgery; Male; Medical sciences; Middle Aged; Oligonucleotide Array Sequence Analysis - methods; Pneumology; Pulmonary Fibrosis - diagnosis; Pulmonary Fibrosis - genetics; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; T-Lymphocytes - physiology; Lung disease; Pneumonia; Intensive care; Respiratory disease; Hypersensitivity; Idiopathic; Gene expression; lung fibrosis; nonspecific interstitial pneumonia; interstitial lung diseases; microarrays; Pulmonary fibrosis; Interstitial pneumonitis; Interstitial; Resuscitation; global transcription analysis
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200504-644OC

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. 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. 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. 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. 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.