alexa In vivo effects of the anti-interleukin-6 receptor inhibitor tocilizumab on the B cell compartment.


Rheumatology: Current Research

Author(s): Roll P, Muhammad K, Schumann M, Kleinert S, Einsele H,

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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 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. Copyright © 2011 by the American College of Rheumatology. This article was published in Arthritis Rheum and referenced in Rheumatology: Current Research

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