B Cell Depletion Therapy in Systemic Lupus Erythematosus: Effect on Autoantibody and Antimicrobial Antibody Profiles

Arthritis Rheum. 2006 Nov;54(11):3612-22. doi: 10.1002/art.22211.

Abstract

Objective: Autoantibody production in patients with systemic lupus erythematosus (SLE) is associated with abnormalities of B cell function and phenotype. Clinical responses to B cell depletion therapy (BCDT), based on rituximab, are encouraging. Therefore, we undertook this study to investigate the effect of BCDT on antibody profiles.

Methods: Serial sera from 16 patients with active, refractory SLE were assayed for antinucleosome antibodies, anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigen, anti-tetanus toxoid, and antibodies to pneumococcal capsular polysaccharide for at least 1 year following BCDT. Anti-dsDNA antibodies derived from the V(H)4.34 immunoglobulin germ line gene (9G4+) were also measured.

Results: All patients achieved peripheral B cell depletion and improved clinically for at least 3 months. Antinucleosome and anti-dsDNA antibodies decreased to a mean +/- SD of 64 +/- 37% and 38 +/- 33% of baseline values, respectively, by 6-8 months post-BCDT. Levels of other autoantibodies and antimicrobial antibodies were generally unchanged. In the 9 of 16 patients who were still well at 1 year, anti-dsDNA antibodies fell to 42 +/- 36% of baseline values at 6-8 months and to 37 +/- 33% at 10-14 months. In patients who had disease flares within 1 year of BCDT, levels of these antibodies decreased to 60 +/- 40% and 83 +/- 93% of baseline values at 6-8 months and at 10-14 months, respectively. Circulating anti-dsDNA antibodies were positive for 9G4 expression in 4 of 6 patients tested, and flares in 2 of these patients were accompanied by rises in 9G4+ anti-dsDNA antibodies.

Conclusion: These observations suggest that B cell clones committed to producing antinucleosome and anti-dsDNA antibodies, including the V(H)4.34 subpopulation of anti-dsDNA antibodies, have a relatively rapid turnover compared with B cell clones producing other antibodies. There was also a trend toward a greater and more sustained decrease in anti-dsDNA antibodies in patients with clinical benefit lasting >1 year.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bacterial / blood
  • Autoantibodies / blood*
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • DNA / immunology
  • Female
  • Humans
  • Leukocyte Reduction Procedures*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / therapy*
  • Male
  • Nucleosomes / immunology

Substances

  • Antibodies, Bacterial
  • Autoantibodies
  • Nucleosomes
  • DNA