Dr. Kleinert has received consulting fees, speaking fees, and/or honoraria from Chugai, Roche, and Abbott (less than $10,000 each).
In vivo effects of the anti–interleukin-6 receptor inhibitor tocilizumab on the B cell compartment
Article first published online: 27 APR 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 5, pages 1255–1264, May 2011
How to Cite
Roll, P., Muhammad, K., Schumann, M., Kleinert, S., Einsele, H., Dörner, T. and Tony, H.-P. (2011), In vivo effects of the anti–interleukin-6 receptor inhibitor tocilizumab on the B cell compartment. Arthritis & Rheumatism, 63: 1255–1264. doi: 10.1002/art.30242
- Issue published online: 27 APR 2011
- Article first published online: 27 APR 2011
- Accepted manuscript online: 18 JAN 2011 12:08PM EST
- Manuscript Accepted: 4 JAN 2011
- Manuscript Received: 5 MAY 2010
- Wilhelm Sander-Stiftung. Grant Number: 2006.037.2
- DFG. Grant Number: SFB 650, Project 16
Interleukin-6 (IL-6) receptor inhibition by tocilizumab was recently licensed for the treatment of rheumatoid arthritis (RA). IL-6 induces in vitro differentiation of B cells into antibody-forming cells; however, the in vivo effects of IL-6 inhibition on the B cell compartment are currently not known. The purpose of this study was to examine this feature.
Sixteen patients with active RA were treated in an open-label study with tocilizumab (8 mg/kg every 4 weeks). Immunophenotyping was performed at baseline, week 12, and week 24.
Memory B cell subsets declined significantly during tocilizumab therapy. Preswitch memory B cells decreased from a median of 19.6% to 12.3% at week 24 and postswitch memory B cells declined from a median of 18.6% to 15.0% at week 24 (P = 0.04). In parallel, CD19+IgA+ and CD19+IgG+ B cells decreased significantly. The proportion of IgA-expressing B cells fell from a median of 9.2% at baseline to 4.3% at week 12 and to 3.6% at week 24 (P = 0.01). IgG+ B cells declined from a median of 6.7% at baseline to 4.9% at week 12 (P = 0.007) and 2.8% at week 24 (P = 0.01). In parallel, serum levels of IgA and IgG were significantly diminished at week 24 (P < 0.05). There was a good correlation between relative and absolute numbers of IgA+ B cells with serum IgA at week 24.
Tocilizumab induced a significant reduction in the frequency of peripheral preswitch and postswitch memory B cells. In addition, the number of IgG+ and IgA+ B cells declined and correlated well with reduced serum immunoglobulin levels. The data indicate that IL-6 blockade affects the B cell hyperreactivity in RA patients.