[The role of cell stress in systemic autoimmune disease]

Anti-DNA antibody is a characteristic feature of systemic lupus erythematosus (SLE) and plays an important role in pathogenesis of lupus nephritis. However, the mechanism of anti-DNA antibody production, which may directly link to the etiology of SLE, remains uncertain. Mammalian DNA alone is not immunogenic. However, some anti-DNA antibodies cross-react with self antigens, and immunization of mice with a certain peptide could induce anti-DNA antibodies. These facts raise a question as to whether an antigenic trigger of anti-DNA antibodies production is DNA itself. Therefore, molecular mimicry of DNA by non DNA antigen is a possibility for the initial production of anti-DNA antibodies. We found that the human monoclonal nephritogenic anti-DNA antibody, O-81, specifically bound to an endoplasmic reticulum stress response protein, Herp. This suggests that lupus nephritogenic anti-DNA antibody cross-react with Herp and an epitope on Herp mimics DNA. Each time cells receive stress (for example, viral infection), the synthesis of Herp protein is induced. If the epitope is immunogenic, repetitive cell stress can be a trigger of anti-DNA antibodies production.