Progress in B-cell Targeting Therapy for the Treatment of Systemic Lupus Erythematosus

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  • TANAKA Yoshiya
    The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health

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Other Title
  • 全身性エリテマトーデスのB細胞標的治療
  • ゼンシンセイ エリテマトーデス ノ B サイボウ ヒョウテキ チリョウ

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Abstract

Systemic lupus erythematosus (SLE) is a representative systemic autoimmune disease characterized by multi-organ manifestation. Although the etiology of the disease remains unclear, the activation of autoreactive T cells and production of antibodies by B cells are mainly involved in the pathological processes of the disease. B cell depletion therapy using anti-CD20 antibody rituximab has shown a rapid onset of effect and prolonged efficacy in refractory SLE, emerging as a promising new agent for the treatment of SLE. We also reported that rituximab is safe for the treatment of active SLE in a domestic pilot study and a multi-center phase Ⅰ/Ⅱ clinical trial. In regard to the mechanism underlying the efficacy of rituximab, it has been reported that the drug caused peripheral depletion of memory B cells and plasma cells. We found that rituximab efficiently depleted naïve and memory B cells and decreased co-stimulatory molecules on B cells and memory T cells. Recovered B cells in patients in long-term remission were dominated by naïve B cells with an increased ratio of naïve T cells, and co-stimulatory molecules remained low. These findings indicate that the reconstitution of the B cell compartment results in the inhibition of T cell activation by memory B cells, which leads to the sustained remission of SLE by rituximab. Although the recent placebo-controlled trials such as EXPLORER with rituximab in SLE did not achieve satisfactory results, other evidence continues to be published in support of the notion that B cell depletion could be useful for refractory SLE. In addition, other B-cell targeted therapies, such as CD22 and agents that interrupt B-T-cell interaction, including belimumab, also have potential of the therapeutic application.

Journal

  • Journal of UOEH

    Journal of UOEH 33 (2), 173-181, 2011

    The University of Occupational and Environmental Health, Japan

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