Identification of a universal B cell epitope on DNA topoisomerase I, an autoantigen associated with scleroderma.
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 beta-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.


CONCLUSIONS
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.
Kato
T
T
Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan.
Yamamoto
K
K
Takeuchi
H
H
Okubo
M
M
Hara
E
E
Nakada
S
S
Oda
K
K
Ito
K
K
Nishioka
K
K
D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004264:DNA Topoisomerases, Type I / Q000276:immunology*; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D008137:Longitudinal Studies; D011994:Recombinant Proteins / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D007141:Immunoglobulin Fc Fragments; D011994:Recombinant Proteins; D004264:DNA Topoisomerases, Type I