Scleroderma (systemic sclerosis) is an autoimmune rheumatic disease of high morbidity and mortality. Much of the clinical burden results from organ-based or vascular fibrosis, and scarring is a pathological hallmark of the disease. It can be regarded s a disease in which there is dysregulated connective tissue repair and inappropriate resolution of fibrosis that has been triggered by inflammation of vascular dysfunction. There is growing evidence to support a genetic basis for the disease that relates to autoimmunity but the basis for altered repair processes is less clear, it appears that there is fibroblast-dependent dysregulated connective tissue repair and this may involve a number of distinct cellular lineages. There are important lessons from developmental biology and also from studies of normal wound healing. Genetic models are no established that replicate key features of scleroderma in mutant mice and some of these provide a platform to explore the broad range of organ based pathologies that occur in the disease, notably lug fibrosis and pulmonary hypertension. Thus fibroblasts in scleroderma are both effecter cells of the disease and also key regulators of normal connective tissue repair. This lecture will explore these issues and review emerging evidence that may permit better understanding of key molecular pathways in scleroderma that could ultimately be targeted as novel forms of disease modifying therapy.
Disclosure of Interest C. Denton Consultant for: Actelion Pharmaceuticals, GSK, Sanofi-Aventis, Serono, Pfizer
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