Ann Rheum Dis. Published Online First: 2 August 2007. doi:10.1136/ard.2007.075762
Extended Report |
Differential effects of epratuzumab on peripheral blood B cells of SLE patients versus normal controls
1 Charité University Hospital, Germany
2 Center for Molecular Medicine and Immunology, Belleville, NJ, USA, United States
3 Charité - Universitätsmedizin Berlin, Germany
4 DRFZ, Germany
5 Charite University Hospital, Germany
6 Charite Univ. Hospital, Germany
* To whom correspondence should be addressed. E-mail: thomas.doerner{at}charite.de.
Accepted 17 July 2007
Abstract
Objective: B-lymphocytes have been implicated in the pathogenesis of lupus and other autoimmune diseases, resulting in the introduction of B-cell-directed therapies. Epratuzumab, a humanized anti-CD22 mAb, is currently in clinical trials, although its effects on patients' B cells are not completely understood.
Methods: This study analyzed the in-vivo effect of epratuzumab on peripheral B-cell subsets in 12 patients with SLE, and also addressed the in-vitro effects of the drug by analyzing anti-Ig-induced proliferation of isolated B cells obtained from the peripheral blood of 11 additional lupus patients and 7 normal subjects.
Results: Upon treatment, a pronounced reduction of CD27- B cells and CD22-surface-expression on CD27- B cells was observed, suggesting that these cells which mainly comprise naïve and transitional B cells are preferentially targeted by epratuzumab in vivo. The results of in-vitro studies indicate additional regulatory effects of the drug by reducing the enhanced activation and proliferation of anti-Ig-stimulated lupus B cells after co-incubation with CD40L or CpG. Epratuzumab inhibited the proliferation of B cells from SLE patients but not normal B cells under all culture conditions.
Conclusions: Epratuzumab preferentially modulates the exaggerated activation and proliferation of B cells from lupus patients in contrast to normal subjects, thus suggesting that epratuzumab might offer a new therapeutic option for patients with SLE, since enhanced B-cell activation is a hallmark of this disease.
Keywords: B cells, CD22, SLE, autoimmunity, biologicals
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