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In vivo effect of the anti interleukin-6 receptor inhibitor tocilizumab on the B-cell compartment.
MedLine Citation:
PMID:  21305508     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: IL-6 receptor inhibition by tocilizumab was recently licensed for the therapy 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. METHODS: Sixteen patients with active rheumatoid arthritis were treated in an open label study with tocilizumab (8mg/kg every 4 weeks). Immunephenotyping was performed at baseline, week 12 and 24. RESULTS: Memory B cell subsets declined significantly during tocilizumab therapy. Pre-switch memory B cells decreased from median 19.6% to 12.3% and post-switch memory B cells declined from 18.6% to 15.0% at week 24 (p=0.04), respectively. In parallel CD19+/IgA+ and IgG+ B cells decreased significantly. The proportion of IgA expressing B cells fell from 9.7% to 4.8% at week 12 (p=0.03) and to 2.7% at week 24 (p=0.004). IgG+ B cells declined from 6.7% to 4.9% (p=0.02) at week 12 and to 2.8% (p=0.006) at week 24. 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 induces a significant frequency reduction of peripheral pre- and post-switch memory B cells. In addition the number of IgG+ and IgA+ B cells declined and correlated well to reduced serum Ig. The data indicate that IL-6 blockade impacts on B cell hyperreactivity of RA patients.
Authors:
Petra Roll; Khalid Muhammad; Mathias Schumann; Stefan Kleinert; Hermann Einsele; Thomas Dörner; Hans-Peter Tony
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-18
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  -     ISSN:  1529-0131     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-2-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 by the American College of Rheumatology.
Affiliation:
Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Berlin, Germany.
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