PT  - JOURNAL ARTICLE
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
TI  - RNA sequencing of transplant-stage idiopathic pulmonary fibrosis lung reveals unique pathway regulation
AID  - 10.1183/23120541.00117-2019
DP  - 2019 Jul 01
TA  - ERJ Open Research
PG  - 00117-2019
VI  - 5
IP  - 3
4099  - http://openres.ersjournals.com/content/5/3/00117-2019.short
4100  - http://openres.ersjournals.com/content/5/3/00117-2019.full
SO  - erjor2019 Jul 01; 5
AB  - 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