Linking VASculopathy and Fibrosis with Autoimmunity in Systemic Sclerosis
The departments Rheumatology and Internal Medicine of the LUMC, together with Galapagos will join forces in a project linking vasculopathy and fibrosis with autoimmunity in Systemic Sclerosis (SSc). The collaboration between the research group of Dr De Vries-Bouwstra (Department of Rheumatology), Prof Van Zonneveld (Department of Internal Medicine) and Galapagos enables application of novel techniques including human microvessel-on-a-chip models and high-through-put assays aiming at target discovery in a large and well-described cohort of SSc patients.
SSc is a severe auto-immune disease that is characterised by excessive fibrosis of the skin and vasculopathy. In addition to skin, several organs, including the heart and lungs can be affected. Prognosis differs between subgroups of patients and is determined by the extent of organ involvement. Patients with a mild form of SSc have a 10-year survival rate of 75%; whereas patients with a severe form have a 10-year survival rate of 55%. Currently, treatment options are limited and a cure for the disease does not exist.
Vascular damage is among the earliest pathological hallmarks of the disease. The discovery of several functional vascular autoantibodies that associate with disease severity and mortality in SSc indicate a link between vasculopathy, autoantibodies and fibrosis. Using the human microvessel-on-a-chip model we will expose human endothelial cells to blood derived from SSc patients to identify which antibodies and/ or other factors cause vascular damage. In addition, transformation of endothelial cells to mesenchymal cells that induce fibrosis after exposure to SSc sera will be studied. High-throughput assays will be applied to identify relevant targets for interfering both with vasculopathy and fibrosis.
In summary, this project aims to understand what causes vasculopathy and fibrosis in SSc to improve prediction of disease outcome and to identify essential factors in the pathogenic process of fibrosis as a starting point for development of novel therapeutics.
