Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system
- Mikiko Tokunaga1,
- Kazuyoshi Saito1,
- Daisuke Kawabata2,
- Yoshitaka Imura2,
- Takao Fujii2,
- Shingo Nakayamada1,
- Shizuyo Tsujimura1,
- Masao Nawata1,
- Shigeru Iwata1,
- Taeko Azuma1,
- Tsuneyo Mimori2,
- Yoshiya Tanaka1
- 1The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyusyu, Japan
- 2Department of Rheumatology and Clinical Immunology, Kyoto University, Graduate School of Medicine, Kyoto, Japan
- Correspondence to:
Dr Y Tanaka
The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka Yahata-nishi, Kitakyushu 807-8555 Japan;
- Accepted 30 October 2006
- Published Online First 15 November 2006
Aim: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious treatment-resistant phenotype of systemic lupus erythematosus. A standard treatment for NPSLE is not available. This report describes the clinical and laboratory tests of 10 patients with NPSLE before and after rituximab treatment, 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 central nervous system-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 >1 year in five patients. Flow cytometric analysis showed that rituximab down regulated CD40 and CD80 on B cells and CD40L, CD69 and inducible costimulator on CD4+ T cells.
Conclusions: Rituximab rapidly improved refractory NPSLE, as evident by resolution of various clinical signs 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. These results warrant further analysis of rituximab as treatment for NPSLE.
- CNS, central nervous system
- FACS, fluorescence-activated cell sorter
- NPSLE, neuropsychiatric systemic lupus erythematosus
- PBS, phosphate-buffered saline
- PE, plasma exchange
- SLE, systemic lupus erythematosus
- SLEDAI, SLE Disease Activity Index
- SPECT, single-photon-emission computed tomography
Published Online First 9 November 2006
Competing interests: None declared.