PT  - JOURNAL ARTICLE
AU  - A M Jacobi
AU  - D M Goldenberg
AU  - F Hiepe
AU  - A Radbruch
AU  - G R Burmester
AU  - T Dörner
TI  - Differential effects of epratuzumab on peripheral blood B cells of patients with systemic lupus erythematosus versus normal controls
AID  - 10.1136/ard.2007.075762
DP  - 2008 Apr 01
TA  - Annals of the Rheumatic Diseases
PG  - 450--457
VI  - 67
IP  - 4
4099  - http://ard.bmj.com/content/67/4/450.short
4100  - http://ard.bmj.com/content/67/4/450.full
SO  - Ann Rheum Dis2008 Apr 01; 67
AB  - 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.