Role of metal-catalyzed oxidation reactions in the early pathogenesis of scleroderma

The observation that revelation of immunocryptic epitopes in self-antigens may initiate the autoimmune response has prompted the search for processes that induce novel autoantigen structure as potential initiators of autoimmunity. Recent studies have demonstrated that the autoantigens targeted in diffuse scleroderma are unified by their enrichment in nucleolini and by their susceptibility to fragmentation in a novel metal-dependent reaction that requires the generation of reactive oxygen species. Several other studies highlight the importance of reactive oxygen species as mediators of damage during ischemia-reperfusion and present evidence for increased generation of these radicals in patients with scleroderma. Together, these studies suggest a model for the pathogenesis of scleroderma in which metals and free radicals play a central, autoamplifying role.