Open AccessLongitudinal analysis of autoantibody response to topoisomerase I in systemic sclerosis
Author(s) -
Kuwana Masataka,
Kaburaki Junichi,
Mimori Tsuneyo,
Kawakami Yutaka,
Tojo Takeshi
Publication year - 2000
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(200005)43:5<1074::aid-anr18>3.0.co;2-e
Subject(s) - autoantibody , antibody , immunology , topoisomerase , epitope , in vivo , group a , isotype , medicine , in vitro , biology , monoclonal antibody , biochemistry , microbiology and biotechnology
Objective To examine serial changes in serum anti–topoisomerase I (anti–topo I) antibody levels in patients with systemic sclerosis (SSc), as well as associations with clinical features and the in vivo activation status of circulating topo I–reactive T and B cells. Methods Serum anti–topo I antibody levels were serially measured at different time points in 28 SSc patients who were positive for anti–topo I antibody at their first visit (range of followup 6–29 years). The patients were subgrouped according to the disappearance (group 1) or persistence (group 2) of anti–topo I antibody. Clinical findings as well as T and B cell responses to topo I were compared between these 2 groups. Results Serum anti–topo I antibody disappeared during the period of followup in 6 patients (group 1), but persisted in 22 patients (group 2). Loss of anti–topo I antibody occurred within 10 years after the first visit and independently of treatment. Group 1 patients had less extensive skin and lung involvement and better survival rates than did group 2 patients. Complete loss of anti–topo I antibody followed a reduction in isotype expression and epitope reactivities. The kinetics of in vitro T cell proliferation induced by topo I were delayed and circulating topo I–reactive T cells were less frequently detected in group 1 versus group 2 patients, suggesting that the disappearance of anti–topo I antibody was due to loss of activation of topo I–reactive T cells. In vitro production of anti–topo I antibody in peripheral blood mononuclear cell cultures in response to antigenic stimulation in both group 1 and group 2 patients indicated persistence of anti–topo I antibody–producing “memory” B cells even after the loss of serum anti–topo I antibody. Conclusion Our results indicate that there is a distinct subset of anti–topo I–positive SSc patients who lose anti–topo I antibody during the disease course and have a favorable outcome. In vivo production of anti–topo I autoantibody may require antigenic stimulation that activates topo I–reactive T and B cells.