Longitudinal analysis of autoantibody response to topoisomerase I in systemic sclerosis.
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.


CONCLUSIONS
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.
Kuwana
M
M
Keio University School of Medicine, Tokyo, Japan.
Kaburaki
J
J
Mimori
T
T
Kawakami
Y
Y
Tojo
T
T
D000917:Antibody Formation; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002452:Cell Count; D018929:Cell Culture Techniques; D004264:DNA Topoisomerases, Type I / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D011379:Prognosis; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000097:blood / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D001323:Autoantibodies; D000939:Epitopes; D004264:DNA Topoisomerases, Type I