Longitudinal analysis of autoantibody response to topoisomerase I in systemic sclerosis

Arthritis Rheum. 2000 May;43(5):1074-84. doi: 10.1002/1529-0131(200005)43:5<1074::AID-ANR18>3.0.CO;2-E.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Formation
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Cell Count
  • Cell Culture Techniques
  • DNA Topoisomerases, Type I / immunology*
  • Epitopes
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology
  • Longitudinal Studies
  • Lymphocyte Activation
  • Prognosis
  • Respiratory Function Tests
  • Scleroderma, Systemic / blood
  • Scleroderma, Systemic / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology


  • Autoantibodies
  • Epitopes
  • DNA Topoisomerases, Type I