Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system
Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system
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DOI：
10.1136/ard.2006.057885
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发表时间：
2007-04-01
影响因子：
27.4
通讯作者：
Tanaka, Yoshiya
中科院分区：
文献类型：
--
作者：
Tokunaga, Mikiko;Saito, Kazuyoshi;Tanaka, Yoshiya
目的：神经精神性系统性红斑狼疮(NPSLE)是一种严重的系统性红斑狼疮耐药表型。目前还没有针对NPSLE的标准治疗方法。本文对10例难治性NPSLE患者进行了利妥昔单抗治疗前后的临床和实验室检查，包括淋巴细胞表型的变化。方法：对10例难治性NPSLE患者在强化治疗的同时给予不同剂量的利妥昔单抗治疗。结果：利妥昔单抗治疗后中枢神经系统相关症状迅速改善，尤其是急性融合状态。利妥昔单抗还改善了所有10名患者在第28天的认知功能障碍、精神病和癫痫发作，并降低了SLE疾病活动指数评分。这些效应在5名患者中持续了1年。流式细胞仪分析显示，利妥昔单抗可下调B细胞表面CD40、CD80的表达，下调CD4(+)T细胞表面的CD40L、CD69及诱导共刺激分子的表达。结论：利妥昔单抗能迅速改善难治性NPSLE患者的临床症状，改善放射学表现。B细胞和T细胞上功能分子的下调表明利妥昔单抗通过共刺激分子调节激活的B细胞和T细胞之间的相互作用。这些结果值得进一步分析利妥昔单抗作为NPSLE的治疗方法。
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.