| Abstract: | Objective. To investigate the distribution of B cell autoepitopes of human DNA topoisomerase I (topo I), an autoantigen associated with scleroderma. Methods. A complementary DNA clone, T1B, was used to produce recombinant proteins of topo I as β-galactosidase fusion proteins. Immunoreactivity to these fusion proteins was then tested in 35 anti–topo I–positive sera from patients with scleroderma, by immunoblotting, enzyme-linked immunosorbent assay, and double immunodiffusion. Results. One epitope was found to be universally recognized by all sera tested. Thirty-two of the samples recognized multiple antigenic regions, but sera from the remaining 3 patients recognized only this universal epitope, and in longitudinal studies of 1 of these 3 patients, the serum recognized only this epitope for more than 2 years, even though multiple, potent, antigenic regions were found on topo I. Conclusion. Recognition of multiple epitopes in most patients suggests that the topo I molecule itself would drive the autoimmunity on topo I. However, antigen-driven autoimmunity could not explain the production of the monoreactive anti–topo I antibody seen in the 3 patients. We thus hypothesize that there is a process whereby recognition of the universal epitope by cross-reaction develops into antigen-driven autoimmunity. |
