title: Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis.
abstract: BACKGROUND
  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.affiliation: Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA.
authors.forename: Moises
authors.initials: M
authors.lastname: Selman
authors.forename: Annie
authors.initials: A
authors.lastname: Pardo
authors.forename: Lourdes
authors.initials: L
authors.lastname: Barrera
authors.forename: Andrea
authors.initials: A
authors.lastname: Estrada
authors.forename: Susan R
authors.initials: SR
authors.lastname: Watson
authors.forename: Keith
authors.initials: K
authors.lastname: Wilson
authors.forename: Natasha
authors.initials: N
authors.lastname: Aziz
authors.forename: Naftali
authors.initials: N
authors.lastname: Kaminski
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000175:diagnosis* / Q000235:genetics*; D001706:Biopsy / Q000379:methods; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007109:Immunity / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D008168:Lung / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011658:Pulmonary Fibrosis / Q000175:diagnosis* / Q000235:genetics*; D013601:T-Lymphocytes / Q000502:physiology