The fibroblast is the target cell in the connective tissue manifestations of Graves' disease

A controversy exists concerning whether the extraocular muscle cell or the fibroblast is the autoimmune target in Graves' ophthalmopathy (GO). Although the extraocular muscle bodies are grossly enlarged in GO, the muscle cells themselves are histologically intact. Within the muscle bodies, as well as in the fatty connective tissue of the orbit, there is an accumulation of glycosaminoglycans (GAG). These hydrophilic mucopolysaccharides are made by fibroblasts. In this commentary, I will present evidence that the fibroblast, and not the extraocular muscle cell, is the autoimmune target in GO and in the other connective tissue manifestations of Graves' disease (pretibial dermopathy and acropachy). This argument is based on clinical evidence, on histochemical and biochemical evidence of fibroblast stimulation in GO, and on functional evidence that patients' orbital lymphocytes recognize autologous orbital fibroblasts, and not eye muscle extract.