吗替麦考酚酯治疗抗富亮氨酸胶质瘤失活蛋白1脑炎的临床与免疫参数观察  

Clinical and immunological analysis of mycophenolate mofetil treatment in anti-leucine-rich glioma-inactivated 1 encephalitis

作　　者：关鸿志[1] 徐晓璐[1] 朱以诚[1] 王斐[2] 范思远[1] 黄颜[1] 金丽日[1] 卢强[1] 任海涛[1] 徐碓 彭斌[1] 崔丽英 Guan Hongzhi , Xu Xiaolu, Zhu Yicheng, Wang Fei, Fan Siyuan, Huang Fan, Jin Liri, Lu Qiang, Ren Haitao, Xu Fan, Peng Bin, Cui Liying.(Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Be~jing 100730, Chin)

机构地区：[1]中国医学科学院北京协和医院神经科,100730 [2]中国医学科学院北京协和医院检验科,100730 [3]中国医学科学院神经科学中心

出　　处：《中华神经科杂志》2018年第4期281-287,共7页Chinese Journal of Neurology

基　　金：首都临床特色应用研究与推广项目（Z161100000516094）

摘　　要：目的分析单中心自身免疫性脑炎队列中接受吗替麦考酚酯（MMF）治疗达到1年的抗富亮氨酸胶质瘤失活蛋白1（LGll）脑炎病例，对其疗效、相关免疫参数和安全性进行评估。方法选择2014年6月至2017年8月在北京协和医院神经科诊治并接受MMF治疗的抗LGll脑炎病例15例。根据北京协和医院《脑炎与副肿瘤综合征登记项目》流程对抗LGll脑炎患者进行评估及随访，每2个月评估改良Rankin量表（mRS）评分，并对血清IgG水平、外周血CD．。阳性B细胞、CD。阳性T细胞和CD。阳性T细胞计数等免疫参数进行评估。采用SPSSV20软件对以上数据进行分析。采用Graphpad Prism6．0软件进行统计绘图。对MMF剂量采用足量诱导期（1．5～3．0g／d）与减量维持期（0．75-2．00g／d）的方案。结果15例患者MMF治疗超过1年，其中13例患者治疗后mRS评分较治疗前好转（mRS评分降低≥1分）。全部患者在随访中均达到良好的神经功能状态（mRS评分≤2分，含复发病例3例）；其中治疗后无症状者9例（9／15，mRS评分=0分）。治疗前中位mRS评分为2（1，3）分，治疗后中位mRS评分为0（0，1）分，差异具有统计学意义（Z=-3．115，P=0．002）。外周血CD19阳性B细胞数治疗前中位数（四分位数）值为320（227，628）×10^6／L[正常值（160～350）×10^6／L]，在MMF治疗过程中，CD19阳性B细胞数呈逐步下降的趋势，至观察终点（12个月）达到最低值[152（105，223）×10^6／L]，较治疗前减低（Z=-2．028，P=0．043）。CD4阳性T细胞数治疗后[1055（802，1072）×10^6／L]与治疗前[1136（736，1432）×10^6／L]比较差异无统计学意义。CD。阳性T细胞数治疗后[568（393，743）×10^6／L]与治疗前[627（413，784）×10^6／L]比较差异无统计学意义。血清IgG治疗前[9．07（6．70，11．32）g／L]与治疗后[8．35（6．63，10．69）g／L]比较差异无统计学意义。在6Objective To evaluate the efficacy and safety of mycophenolate mofetil （MMF） in anti- leucine-rich glioma-inaetivated 1 （ LGI1 ） encephalitis by analyzing the clinical and immunologic data of patients treated with MMF in this prospective cohort of anti-LGI1 encephalitis. Methods Patients treated with MMF for more than one year in Peking Union Medical College Hospital were included in this study.MMF was given at a dosage of 1.5 - 3.0 g/d in the induction period （ two to four months） and 0. 75 - 2.00 g/d in the maintenance period. All the patients were followed up regularly. Modified Rankin Scale （mRS） score evaluation, serum IgG and peripheral CDig-positive B cells, CD4-positive T cells and CDs-positive T ceils testing were performed every two months. Results Fifteen patients were included in this study who received first-line immunotherapy combined with MMF. No other second-fine therapy including rituximab was used. Thirteen patients responded well to MMF combined with first-line immunotherapy （a decrease in mRS score of more than 1 ）. All 15 patients had a good outcome （ i. e. , a mRS score of 0 - 2） , including nine patients without residual symptoms （a mRS score of 0）. After 12 months of MMF treatment, CDl9-positive B cells were significantly decreased （median 320 （227, 628） × 10^6/L vs 152 （105, 223） × 10^6/L; Z= -2.028,P=0.043）, while serum IgG （9.07 （6.70, 11.32） g/Lvs 8.35 （6.63, 10.69） g/L, P= 0. 144））, CD4positive T cells （1 136 （736, 1 432） ×10^6/Lvs 1 055 （802, 1 072） × 10^6/L, P =0. 866） and CDs-positive T ceils （627 （413, 784）×10^6/L vs 568 （393, 743） × 10^6/L, P=0.735） were not significantly changed. Three patients relapsed and were treated with additional cycle of first-line immunotherapy and increased dosage of MMF （ induction dosage） resulting in remission. CDi9-positive B cells were tested to be increased during the patients＇ relapse. No serious adverse event was noted in all these patients. Conclusions MMF

关 键 词：脑炎 自身免疫 富亮氨酸胶质瘤失活蛋白1 吗替麦考酚酯 免疫疗法 B淋巴细胞 

分 类 号：R739.41[医药卫生—肿瘤] R742.9[医药卫生—临床医学]