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Efficacy of rituximab (Anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system
  1. Mikiko Tokunaga (mikiko-m{at}med.uoeh-u.ac.jp)
  1. University of Occupational & Environmental Health, Japan
    1. Kazuyoshi Saito (kazu-s{at}med.uoeh-u.ac.jp)
    1. University of Occupational & Environmental Health, Japan
      1. Daisuke Kawabata (daisuke{at}kuhp.kyoto-u.ac.jp)
      1. Kyoto University, Graduate School of Medicine, Japan
        1. Yoshitaka Imura (yimura{at}kuhp.kyoto-u.ac.jp)
        1. Kyoto University, Graduate School of Medicine, Japan
          1. Takao Fujii (takfujii{at}kuhp.kyoto-u.ac.jp)
          1. Kyoto University, Graduate School of Medicine, Japan
            1. Shingo Nakayamada (s-nakaya{at}med.uoeh-u.ac.jp)
            1. University of Occupational and Environmental Health, Japan
              1. Shizuyo Tsujimura (s35-a721{at}med.uoeh-u.ac.jp)
              1. University of Occupational and Environmental Health, Japan
                1. Masao Nawata (m-nawata{at}med.uoeh-u.ac.jp)
                1. University of Occupational and Environmental Health, Japan
                  1. Shigeru Iwata (s-iwata{at}med.uoeh-u.ac.jp)
                  1. University of Occupational and Environmental Health, Japan
                    1. Taeko Azuma (t-azuma{at}med.uoeh-u.ac.jp)
                    1. University of Occupational and Environmental Health, Japan
                      1. Tsuneyo Mimori (mimorit{at}kuhp.kyoto-u.ac.jp)
                      1. Kyoto University, Graduate School of Medicine, Japan
                        1. Yoshiya Tanaka (tanaka{at}med.uoeh-u.ac.jp)
                        1. University of Occupational and Environmental Health, Japan

                          Abstract

                          Purpose: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious, treatment-resistant phenotype of SLE. There is no standard therapy for NPSLE. In this report, we describe the clinical and laboratory tests of 10 NPSLE patients before and after rituximab therapy, including changes in lymphocyte phenotypes.

                          Methods: Rituximab was administered at different doses in 10 patients with refractory NPSLE despite intensive treatment.

                          Results: Treatment with rituximab resulted in rapid improvement of CNS-related manifestations, particularly acute confusional state. Rituximab also improved cognitive dysfunction, psychosis, and seizure, and reduced the SLE Disease Activity Index score at Day 28 in all 10 patients. These effects lasted for more than a year in 5 patients. Flow cytometric analysis showed that rituximab down-regulated CD40 and CD80 on B cells and CD40L, CD69, and inducible costimulator (ICOS) on CD4+ T cells.

                          Conclusions: Rituximab rapidly improved refractory NPSLE, as evident by resolution of various clinical sings and symptoms and improvement of radiographic findings. The down-regulation of functional molecules on B and T cells suggests that rituximab modulates the interaction of activated B and T cells through costimulatory molecules. Our results warrant further analysis of rituximab as treatment for NPSLE.

                          • CD40
                          • CD80
                          • neuropsychiatric systemic lupus erythematosus
                          • rituximab
                          • systemic lupus erythematosus

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