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