DNA antibody idiotypes: a review of their genetic, clinical, and immunopathologic features

The initial studies of anti-DNA antibody idiotypes we performed, along with those of our colleagues and other groups, focused on the narrow question of their relevance to lupus autoantibodies. The subsequent studies in this report have forced us to examine a much broader range of issues. It is evident that despite the great advances in understanding the structure and function of antibodies, lymphocytes, and receptors, our knowledge of many fundamental elements in autoimmune disease is woefully incomplete. We are still unsure whether the germ line gene sequences controlling antibody production have evolved solely in response to exposure to new foreign antigens. Alternatively, these antibodies (and the idiotypes they bear) may have developed largely in response to changes in the internal environment. Superficially, it can be argued that "self reactivity" associated with the clinical expression of a disease results from a combination of immunologic, genetic, hormonal, and environmental elements. For example, the expression of the 16/6 Id in an appropriate setting may have pathogenetic consequences for some individuals. However, our knowledge of the precise sequence of events that result in devastating disease for some but minimal disease for others is just one of the remaining mysteries.