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 hypothesis 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 antigen, could be explained if both the presence of the antigen and severe oxidative stress is required, before tissue destruction occurs. Furthermore, the cyclic nature of tissue destruction and problems with detecting robust high affinity autoreactivity to self antigens may be easier to understand if we presume that pathological autoreactivity is targeting redoxmodified self antigens, while assays to unmodified self only measure its cross-reactivity to normal self antigens.