Longitudinal analysis of autoantibody response to topoisomerase I in systemic sclerosis

Masataka Kuwana, Junichi Kaburaki, Tsuneyo Mimori, Yutaka Kawakami, Takeshi Tojo

Research output: Contribution to journalArticle

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Abstract

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 I 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 I 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.

Original languageEnglish
Pages (from-to)1074-1084
Number of pages11
JournalArthritis and Rheumatism
Volume43
Issue number5
DOIs
Publication statusPublished - 2000 May

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Type I DNA Topoisomerase
Systemic Scleroderma
Autoantibodies
Antibodies
T-Lymphocytes
B-Lymphocytes
Serum

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Longitudinal analysis of autoantibody response to topoisomerase I in systemic sclerosis. / Kuwana, Masataka; Kaburaki, Junichi; Mimori, Tsuneyo; Kawakami, Yutaka; Tojo, Takeshi.

In: Arthritis and Rheumatism, Vol. 43, No. 5, 05.2000, p. 1074-1084.

Research output: Contribution to journalArticle

Kuwana, Masataka ; Kaburaki, Junichi ; Mimori, Tsuneyo ; Kawakami, Yutaka ; Tojo, Takeshi. / Longitudinal analysis of autoantibody response to topoisomerase I in systemic sclerosis. In: Arthritis and Rheumatism. 2000 ; Vol. 43, No. 5. pp. 1074-1084.
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