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108 Iguratimod inhibits human b cell terminal differentiation in vitro and may benefit patients with refractory lupus nephritis
  1. Q Yan1,
  2. Y Ye1,
  3. X Zhang2 and
  4. C Bao1
  1. 1RenJi Hospital- School of Medicine- Shanghai JiaoTong University, Rheumatology, Shanghai, China
  2. 2Chinese Academy of Sciences, Institute Pasteur of Shanghai, Shanghai, China

Abstract

Background and Aims Iguratimod (IGT) is a small molecular immunomodulatory drug and has been approved for treating rheumatoid arthritis. In our previous work, IGT ameliorates lupus-like disease in MRL/lpr mice by inhibiting abnormal B cell differentiation. The aim of this study is to further investigate the effects of IGT on human B cells.

Methods We established a set of stimulations to induce naive human B cell into plasmablast (PB) in vivo. We also enrolled 7 patients with refractory lupus nephritis (LN) to assess the potential efficacy of IGT.

Results IGT significantly attenuates the generation of CD19+CD20-CD27hiCD38hi plasma cells upon both BCR-dependent and independent stimulations. IGT affects neither proliferation or apoptosis of B cell in vitro. In further investigation on B cell differentiation signalling pathwasys, we identifies that Blimp-1 and Xbp-1 can be remarkably impaired by IGT both in transcriptional and protein level; while Jak/STAT or NF-κB signalling are intact with IGT treatment. For explosive clinical study, seven patients with refractory LN were enrolled and administrated with IGT and steroids. ALL of these patients surprisingly show improved proteinuria after 8 week treatment. One patient quit the treatment because of anaemia.

Conclusions IGT has a unique effect to arrest B cell terminal differentiation, which provides strong evidence that this drug could be a new candidate drug to treat B cell related autoimmune diseases such as lupus.

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