Immune dysfunction in Systemic Sclerosis Interstitial Lung Disease
Research type
Research Study
Full title
Immune dysfunction in Systemic Sclerosis Interstitial Lung Disease: A patient-relevant disease model for novel drug development in SSc-ILD
IRAS ID
320117
Contact name
Paul Minnis
Contact email
Sponsor organisation
Northern Health and Social Care Trust
Duration of Study in the UK
0 years, 7 months, 4 days
Research summary
Systemic sclerosis (SSc) is a severe auto-immune disease, occurring in up to 20 people per 100,000. Women are up to nine times more affected than men resulting in disproportionate morbidity and mortality. Inflammation, vasculopathy, and fibrosis are key hallmarks of SSc. Approximately 30–40% of patients develop clinically significant lung fibrosis (SSc-ILD) with limited therapeutic options. Importantly, over 40% of patients with SSc-ILD die within 10 years of diagnosis, strongly identifying an unmet need for further research into mechanisms of fibrosis, in particular for novel drug development.
Animal models have been used to investigate fibrotic development in SSc, however these studies have significant limitations therefore there is an urgent need for patient-relevant in vitro models to examine disease pathogenesis, screen appropriate treatment regimens, and identify new targets for treatment.
We wish to establish a novel pre-clinical model using peripheral blood derived induced pluripotent stem cells (iPSCs) differentiated fibroblasts from SSC-ILD patients to investigate the mechanisms of fibrosis, and identify targets for treatment. Our study will provide an in-depth analysis of the role of epithelial lung injury to the pathogenesis of SS-ILD. In particular we will focus on the role of epithelial HE4 and hypoxia on A20 induced immune dysregulation.REC name
West of Scotland REC 3
REC reference
23/WS/0033
Date of REC Opinion
13 Feb 2023
REC opinion
Further Information Favourable Opinion