• Ivana V Yang, Leah G Luna, Jennifer Cotter, Janet Talbert, Sonia M Leach, Raven Kidd, Julia Turner, Nathan Kummer, Dolly Kervitsky, Kevin K Brown, Kathy Boon, Marvin I Schwarz, David A Schwartz, and Mark P Steele.
• Center for Genes, Environment and Health, National Jewish Health, Denver, Colorado, United States of America.
• Plos One. 2012 Jan 1;7(6):e37708.

RationalePeripheral blood biomarkers are needed to identify and determine the extent of idiopathic pulmonary fibrosis (IPF). Current physiologic and radiographic prognostic indicators diagnose IPF too late in the course of disease. We hypothesize that peripheral blood biomarkers will identify disease in its early stages, and facilitate monitoring for disease progression.MethodsGene expression profiles of peripheral blood RNA from 130 IPF patients were collected on Agilent microarrays. Significance analysis of microarrays (SAM) with a false discovery rate (FDR) of 1% was utilized to identify genes that were differentially-expressed in samples categorized based on percent predicted D(L)CO and FVC.Main Measurements And ResultsAt 1% FDR, 1428 genes were differentially-expressed in mild IPF (D(L)CO >65%) compared to controls and 2790 transcripts were differentially- expressed in severe IPF (D(L)CO >35%) compared to controls. When categorized by percent predicted D(L)CO, SAM demonstrated 13 differentially-expressed transcripts between mild and severe IPF (< 5% FDR). These include CAMP, CEACAM6, CTSG, DEFA3 and A4, OLFM4, HLTF, PACSIN1, GABBR1, IGHM, and 3 unknown genes. Principal component analysis (PCA) was performed to determine outliers based on severity of disease, and demonstrated 1 mild case to be clinically misclassified as a severe case of IPF. No differentially-expressed transcripts were identified between mild and severe IPF when categorized by percent predicted FVC.ConclusionsThese results demonstrate that the peripheral blood transcriptome has the potential to distinguish normal individuals from patients with IPF, as well as extent of disease when samples were classified by percent predicted D(L)CO, but not FVC.

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