Rosen A, Casciola-Rosen L, Wigley F
Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Curr Opin Rheumatol. 1997 Nov;9(6):538-43. doi: 10.1097/00002281-199711000-00010.
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.
自身抗原中免疫隐蔽表位的暴露可能引发自身免疫反应这一观察结果，促使人们寻找诱导新的自身抗原结构的过程，将其作为自身免疫的潜在启动因素。最近的研究表明，弥漫性硬皮病中靶向的自身抗原具有共同特征，即它们在核仁素中富集，并且在一种需要产生活性氧的新型金属依赖性反应中易于断裂。其他几项研究强调了活性氧作为缺血再灌注损伤介质的重要性，并提供证据表明硬皮病患者体内这些自由基的生成增加。这些研究共同提出了一种硬皮病发病机制模型，其中金属和自由基起着核心的、自我放大的作用。
