Anti-IL-6 receptor antibody (tocilizumab): a B cell targeting therapy

CER4371
2011 Vol.29, N°4
PI 0697, PF 0700
Brief Papers

Free to view
(click on article PDF icon to read the article)

PMID: 21813064 [PubMed]

Received: 08/12/2010
Accepted : 08/03/2011
In Press: 01/09/2011
Published: 01/09/2011

Abstract

BACKGROUND: IL-6 mediated inflammation is induced by binding to IL-6 receptor (IL-6R) or IL-6/IL-6R complex binding gp130. Tocilizumab, a recombinant humanised monoclonal antibody that acts as IL-6R antagonist has been recently introduced for the treatment of rheumatoid arthritis (RA). OBJECTIVES:
To evaluate whether tocilizumab therapy may induce B cells to undergo phenotypic changes compatible with regulatory function.
METHODS:
B cells from treated RA patients were isolated before and after 3 months of treatment with tocilizumab and were stained for the expression of intracellular TGF-β, IL-10, membrane CD69, and MHCII. These markers were assessed in CD25high B cells considered to belong to a regulatory/suppressive subset of B cells. All markers were expressed in mean flow cytometry intensity (MFI), with results given in mean ± SEM. Data was compared before and after tocilizumab treatment.
RESULTS:
Clinical improvement was noted three months following the initiation of tocilizumab, namely: DAS improvement from 6.8±0.3 at baseline to 3.1±0.4, p<0.002, and ESR decrease from 44.4±8.6 at baseline to 7.4±2.3, p<0.006. This clinical benefit was found to occur in association with the expansion of a B cell subset with regulatory properties namely: the expression of intracellular TGF-β in CD25-high B cells was significantly increate (from 5.2±2.3 at baseline to 8.1±2.8; p<0.02); In addition, the expression of MHC-II and of CD69 on B cells were significantly reduced (from 9.1±2.2 at baseline to 4.2±0.4; p<0.04), and (from 7.6±2.4 at baseline to 2.7±0.7; p<0.03) respectively.
CONCLUSIONS:
The present finding of a shift in B cell properties following tocilizumab treatment, namely the increase in TGF-β expression and the alteration in the activation status (CD69 expression) and APC properties (MHC-II expression) in CD25high B cells, suggests that the induction/expansion of B regulatory cells may be one of the mechanisms by which tocilizumab may possibly produce its beneficial clinical effects.