In vivo effects of the anti–interleukin‐6 receptor inhibitor tocilizumab on the B cell compartment

P Roll, K Muhammad, M Schumann… - Arthritis & …, 2011 - Wiley Online Library
P Roll, K Muhammad, M Schumann, S Kleinert, H Einsele, T Dörner, HP Tony
Arthritis & Rheumatism, 2011Wiley Online Library
Abstract Objective 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.
Methods 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 …
Objective
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.
Methods
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.
Results
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.
Conclusion
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.
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