TY - JOUR T1 - RNA sequencing of transplant-stage idiopathic pulmonary fibrosis lung reveals unique pathway regulation JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00117-2019 VL - 5 IS - 3 SP - 00117-2019 AU - Pitchumani Sivakumar AU - John Ryan Thompson AU - Ron Ammar AU - Mary Porteous AU - Carly McCoubrey AU - Edward Cantu III AU - Kandasamy Ravi AU - Yan Zhang AU - Yi Luo AU - Denis Streltsov AU - Michael F. Beers AU - Gabor Jarai AU - Jason D. Christie Y1 - 2019/07/01 UR - http://openres.ersjournals.com/content/5/3/00117-2019.abstract N2 - Idiopathic pulmonary fibrosis (IPF), the scarring of lung parenchyma resulting in the loss of lung function, remains a fatal disease with a significant unmet medical need. Patients with severe IPF often develop acute exacerbations resulting in the rapid deterioration of lung function, requiring transplantation. Understanding the pathophysiological mechanisms contributing to IPF is key to develop novel therapeutic approaches for end-stage disease.We report here RNA-sequencing analyses of lung tissues from a cohort of patients with transplant-stage IPF (n=36), compared with acute lung injury (ALI) (n=11) and nondisease controls (n=19), that reveal a robust gene expression signature unique to end-stage IPF. In addition to extracellular matrix remodelling pathways, we identified pathways associated with T-cell infiltration/activation, tumour development, and cholesterol homeostasis, as well as novel alternatively spliced transcripts that are differentially regulated in the advanced IPF lung versus ALI or nondisease controls. Additionally, we show a subset of genes that are correlated with percent predicted forced vital capacity and could reflect disease severity.Our results establish a robust transcriptomic fingerprint of an advanced IPF lung that is distinct from previously reported microarray signatures of moderate, stable or progressive IPF and identifies hitherto unknown candidate targets and pathways for therapeutic intervention in late-stage IPF as well as biomarkers to characterise disease progression and enable patient stratification.An RNA-Seq-based transcriptomic fingerprint of severe IPF enriched in pathways of T-cell infiltration/activation, tumour development and cholesterol homeostasis highlights novel splice variants, candidate targets and biomarkers in advanced IPF http://bit.ly/2YbTOv8 ER -