Oxidative Stress, Altered-Self and Autoimmunity

Abstract

It is well known that oxidative stress can induce production of free radicals that can modify proteins. The hy-pothesis presented here is that the target antigens in autoimmune diseases, such as type 1 diabetes mellitus, are not normal self proteins but rather self proteins that have been altered by free radicals, produced as a result of oxidative stress in the target cells. The observation that disease often occurs only in a single tissue, even when other tissues contain the same an-tigen, could be explained if both the presence of the antigen and severe oxidative stress is required, before tissue destruc-tion occurs. Furthermore, the cyclic nature of tissue destruction and problems with detecting robust high affinity autoreac-tivity to self antigens may be easier to understand if we presume that pathological autoreactivity is targeting redox-modified self antigens, while assays to unmodified self only measure its cross-reactivity to normal self antigens.