Journal
ANNALS OF THE RHEUMATIC DISEASES
Volume 70, Issue 8, Pages 1507-1510Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/ard.2010.141325
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Categories
Funding
- Wilhelm Sanderstiftung [2006.037.2]
- Roche
- Abbott
- Chugai
- Wyeth
- Genentech
- Immunomedics
- UCB
- [16]
- [SFB 650]
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Objective Interleukin 6 (IL-6) receptor (IL-6R) inhibition by tocilizumab is a novel anti-inflammatory therapy for rheumatoid arthritis (RA) patients. As IL-6 is a late differentiation factor of B cells the authors asked if IL-6R inhibition impacts on the mutational differentiation of human memory B-cell antigen receptors in vivo. Methods 1733 immunoglobulin receptors (IgR) of single cell sorted preswitch and postswitch memory B cells were prospectively analysed from 11 RA patients under IL-6R inhibition (7 patients) or tumour necrosis factor (TNF) inhibition (4 patients). Results The results show a reduced mutational frequency in IgR of preswitch memory B cells (p = 0.0001) during week 12, week 24 and 1 year of tocilizumab therapy. Mutational hotspot RGYW/WRCY motifs indicated significantly decreased targeting (p < 0.05) in preswitch and postswitch memory B cells. Anti-TNF alpha therapy had no effect on mutational frequency and mutational hotspot targeting motifs in memory B-cell subsets. Conclusions These data suggest that preswitch and postswitch memory B cells are susceptible to IL-6R inhibition in vivo. Acquisition of mutations was substantially altered in preswitch memory B cells, while targeting of mutational hotspots affected preswitch and postswitch memory B cells. The results indicate that preswitch and postswitch memory B cells have a differential dependence on the IL-6/IL-6R system for differentiation, which can be influenced by tocilizumab in vivo.
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