EXTENDED REPORTS

Differential effects of epratuzumab on peripheral blood B cells of patients with systemic lupus erythematosus versus normal controls

A M Jacobi¹, D M Goldenberg², F Hiepe^1,3, A Radbruch³, G R Burmester¹, T Dörner^1,3,4

¹ Charite Centrum 12, Charite University Medicine, Berlin
² Center for Molecular Medicine and Immunology, Belleville, NJ, USA
³ German Center for Rheumatology Research (DRFZ), Berlin, Germany
⁴ Centrum 14, Charite University Medicine

ProfessorDr Thomas Dörner, ChariteCenter 14, Charite Universitätsmedizin Berlin, Chariteplatz 01, 10098 Berlin, Germany; thomas.doerner{at}charite.de

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 humanised anti-CD22 monoclonal antibody, is currently in clinical trials, although its effects on patients’ B cells are not completely understood.

Methods: This study analysed the in vivo effect of epratuzumab on peripheral B cell subsets in 12 patients with systemic lupus erythematosus, and also addressed the in vitro effects of the drug by analysing anti-immunoglobulin-induced proliferation of isolated B cells obtained from the peripheral blood of 11 additional patients with lupus and seven 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-immunoglobulin-stimulated lupus B cells after co-incubation with CD40L or CpG. Epratuzumab inhibited the proliferation of B cells from patients with systemic lupus erythematosus but not normal B cells under all culture conditions.

Conclusions: Epratuzumab preferentially modulates the exaggerated activation and proliferation of B cells from patients with lupus in contrast to normal subjects, thus suggesting that epratuzumab might offer a new therapeutic option for patients with systemic lupus erythematosus, as enhanced B cell activation is a hallmark of this disease.

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