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Differential effects of epratuzumab on peripheral blood B cells of SLE patients versus normal controls
  1. Annett M. Jacobi (annett.jacobi{at}charite.de)
  1. Charité University Hospital, Germany
    1. David M. Goldenberg (dmg.gscancer{at}worldnet.att.net)
    1. Center for Molecular Medicine and Immunology, Belleville, NJ, USA, United States
      1. Falk T. Hiepe (falk.hiepe{at}charite.de)
      1. Charité - Universitätsmedizin Berlin, Germany
        1. Andreas Radbruch (radbruch{at}drfz.de)
        1. DRFZ, Germany
          1. Gerd R. Burmester (gerd.burmester{at}charite.de)
          1. Charite University Hospital, Germany
            1. Thomas Dörner (thomas.doerner{at}charite.de)
            1. Charite Univ. Hospital, Germany

              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.

              • B cells
              • CD22
              • SLE
              • autoimmunity
              • biologicals

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