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减少剂量利妥昔单抗治疗抗 N-甲基-D-天冬氨酸受体脑炎:中国患者的观察性研究。

Reduced dosage rituximab in the treatment of anti-N-methyl-d-aspartate receptor encephalitis: An observation study in Chinese patients.

机构信息

Department of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.

Institute of Neurology, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.

出版信息

J Neuroimmunol. 2019 May 15;330:81-86. doi: 10.1016/j.jneuroim.2019.02.008. Epub 2019 Feb 18.

Abstract

The aim of this study was to observe the treatment effect and investigate the possible mechanism of reduced dosage (600 mg) rituximab treatment on anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. The median modified Rankin Scale of ten enrolled patients decreased from 4 (range 2-4) before rituximab infusion to 0 (range 0-2) after a mean follow-up time of 24.3 ± 8.7 months. One patient relapsed 9 months after treatment. No severe adverse event was observed. The proportion of total B cells in lymphocytes was depleted from 13.4 ± 6.7% to 0.6 ± 0.8% one day after treatment. B cells started to regeneration at 3 months and reached 9.4 ± 3.7% at 12 months after treatment. At this time point, proportion of regulatory B cells (Breg) in reconstituted B cells was significantly higher than that before treatment (15.3 ± 12.1% vs. 0.5 ± 0.6%, p = 0.006), while proportion of memory B cells (Bmem) was significantly lower than baseline level (8.0 ± 4.5% vs. 30.2 ± 12.6%, p < 0.001). Our results supported that reduced dosage rituximab was effective and safe in treating anti-NMDAR encephalitis. B cell depletion and rebalance of Breg and Bmem might be involved in the treatment mechanism of this therapy.

摘要

本研究旨在观察降低剂量(600mg)利妥昔单抗治疗抗 N-甲基-D-天冬氨酸受体(抗 NMDAR)脑炎的疗效,并探讨可能的作用机制。纳入的 10 例患者的中位改良 Rankin 量表评分在利妥昔单抗输注前为 4 分(范围 2-4 分),随访 24.3±8.7 个月后降至 0 分(范围 0-2 分)。1 例患者在治疗后 9 个月复发。未观察到严重不良事件。治疗后 1 天,淋巴细胞中总 B 细胞的比例从 13.4±6.7%降至 0.6±0.8%,3 个月后开始再生,治疗后 12 个月时达到 9.4±3.7%。此时,再生 B 细胞中调节性 B 细胞(Breg)的比例明显高于治疗前(15.3±12.1%比 0.5±0.6%,p=0.006),而记忆 B 细胞(Bmem)的比例明显低于基线水平(8.0±4.5%比 30.2±12.6%,p<0.001)。我们的结果支持降低剂量利妥昔单抗治疗抗 NMDAR 脑炎有效且安全。B 细胞耗竭以及 Breg 和 Bmem 的平衡可能参与了该治疗的作用机制。

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