Defective repair of 0(6)-methylguanine in autoimmune diseases.

On the premise that somatic mutations may be involved in the pathogenesis of diseases such as systemic lupus erythematosus and rheumatoid arthritis, the proficiency of repair of 0(6)-methylguanine, a powerful, premutagenic, directly miscoding base lesion, was examined in the DNA of peripheral-blood mononuclear cells (mainly lymphocytes) from patients with such diseases. The capacity of lymphocytes to repair this lesion was impaired in many patients with autoimmune disease. In some healthy controls repair was also defective whereas in other, nonautoimmune diseases, it was not. These findings support the hypothesis that this defect of repair was not simply a result of the disease state. It is therefore postulated that defective repair of 0(6)-methylguanine could be one of the factors determining the susceptibility of autoimmune diseases in genetically predisposed individuals.