Dr. Teodorescu owns stock and/or holds stock options in TheraTest Laboratories. Dr. Edwards has received consulting fees and/or honoraria (less than $10,000) from Roche.
B cell depletion therapy in systemic lupus erythematosus: Effect on autoantibody and antimicrobial antibody profiles
Article first published online: 30 OCT 2006
Copyright © 2006 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 54, Issue 11, pages 3612–3622, November 2006
How to Cite
Cambridge, G., Leandro, M. J., Teodorescu, M., Manson, J., Rahman, A., Isenberg, D. A. and Edwards, J. C. (2006), B cell depletion therapy in systemic lupus erythematosus: Effect on autoantibody and antimicrobial antibody profiles. Arthritis & Rheumatism, 54: 3612–3622. doi: 10.1002/art.22211
- Issue published online: 30 OCT 2006
- Article first published online: 30 OCT 2006
- Manuscript Accepted: 9 AUG 2006
- Manuscript Received: 13 FEB 2006
- Arthritis Research Campaign (UK)
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.
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 VH4.34 immunoglobulin germ line gene (9G4+) were also measured.
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.
These observations suggest that B cell clones committed to producing antinucleosome and anti-dsDNA antibodies, including the VH4.34 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.