Raynaud's phenomenon and scleroderma
Systemic sclerosis (SSc) is an autoimmune disease characterized by the fibrosis of different organs including the skin, lungs and gut. Vasculopathy is another primary feature of this rare but severe disease. Both may be linked from a pathogenesis point of view; however, neither the precise nature of the mechanism nor the ensuing therapeutic targets are known. Recent studies have identified interleukin (IL)13 as a key downstream mediator in the development of fibrosis. At the genetic level, genes involved in wound healing and fibrosis are linked to the Th2-associated cytokines IL4, IL5 and IL13. Accordingly, IL13 promotes the differentiation of fibroblasts into myofibroblasts and the production of extracellular matrix components such as collagen. Finally, IL13 expression increases in SSc mouse models and in SSc patients.
Abnormalities of endothelial cells are thought to occur very early in the course of the disease. The fact that Raynaud phenomenon often precedes the other symptoms is one of the arguments for this hypothesis.
Early intervention on vasculopathy could prevent fibrosis and irreversible damages to happen.
In UMR-CNRS5164, one of our major axis is to find the link between autoimmunity, vascular damages and fibrosis in scleroderma.