FCGR3A基因多态性影响利妥昔单抗治疗视神经脊髓炎谱系疾病患者疗效的分析  

Analysis of the impact of FCGR3A gene polymorphism on the efficacy of rituximab treatment in neuromyelitis optica spectrum disorder patients

作　　者：张伟赫[1] 崔蕾[1] 张晔琼 王璐[1] 孙丽丽[1] 焦劲松[1] 彭丹涛[1] 矫毓娟[1] ZHANG Weihe;CUI Lei;ZHANG Yeqiong;WANG Lu;SUN Lili;JIAO Jinsong;PENG Dantao;JIAO Yujuan(不详;Department of Neurology,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]中日友好医院神经内科,100029

出　　处：《中国神经免疫学和神经病学杂志》2023年第6期400-405,共6页Chinese Journal of Neuroimmunology and Neurology

基　　金：中日友好医院院级课题(2019-1-QN-51)。

摘　　要：目的探讨利妥昔单抗(RTX)治疗视神经脊髓炎谱系疾病(NMOSD)的疗效及其与FCGR3A基因多态性的关系。方法对中日友好医院神经内科收治的4例携带FCGR3A-F型基因并接受常规剂量RTX治疗后复发的血清水通道蛋白4抗体(AQP4-IgG)阳性NMOSD病例的临床特点、外周血CD19^(+)B细胞水平及基因多态性进行回顾性分析。结果男1例、女3例,发病年龄分别为30、35、42和68岁,其中3例为FCGR3A-FF型,1例为FCGR3A-VF型。3例FF型中2例患者及1例VF型患者应用RTX前经历2次以上发作,1例FF型为首次发作。3例FF型患者RTX后首次复发时间分别为1.5、2.0及8.5个月,1例VF型患者首次复发时间为20.0个月。3例FF型患者中2例于RTX诱导治疗后1.5和2.0个月复发,1例于第二轮RTX后2.5个月复发;1例VF型患者于第4轮RTX后2.0个月复发。2例FF型患者更换为吗替麦考酚酯(1000 mg 2次/d)口服,随访1年余未再复发;1例FF型和1例VF型患者依据外周血CD19^(+)B细胞水平缩短RTX重复间期,随访8.0个月余未复发。2例FF型和1例VF型患者CD19^(+)B细胞水平分别于RTX治疗后1.5~2.5个月快速回升至3、21和1个/μL。结论携带FCGR3A-FF型基因的NMOSD患者在接受RTX治疗后复发风险较高,首次复发时间较短,建议针对这类患者调整治疗方案或考虑使用其他免疫抑制药物。Objective To investigate the efficacy of rituximab(RTX)on neuromyelitis optica spectrum disorder(NMOSD)and its association with FCGR3A gene polymorphism.Methods A retrospective analysis was conducted on clinical characteristics,peripheral blood CD19^(+)B cell levels,and genetic polymorphism in four cases of FCGR3A-F genotype individuals with serum AQP4-IgG antibody-positive NMOSD who experienced relapse after standard-dose RTX treatment at the Neurology Department of the China-Japan Friendship Hospital.Results Among the cases,there were one male and three female patients,with onset ages of 30,35,42,and 68 years.Three cases exhibited the FCGR3A-FF genotype,while one case displayed the FCGR3A-VF genotype.Two out of three FF genotype patients and one VF genotype patient experienced more than two attacks before RTX application,while one FF genotype patient experienced the initial attack.The time to first relapse post-RTX treatment was 1.5,2.0,and 8.5 months for three FF genotype patients and 20 months for the VF genotype patient.Among the three FF genotype patients,two relapsed at 1.5 and 2.0 months after RTX induction therapy respectively,and one relapsed after the second round of RTX treatment at 2.5 months.The VF genotype patient relapsed after the fourth round of RTX at 2.0 months.Two FF genotype patients switched to oral azathioprine(1000 mg twice daily)and remained relapse-free for over a year;one FF genotype and one VF genotype patient adjusted the RTX repetition interval based on peripheral blood CD19^(+)B cell levels and remained relapse-free for over 8 months.In two FF genotype and one VF genotype patient,CD19^(+)B cell levels rapidly rebounded to 3,21,and 1 cells/μL,respectively,1.5 to 2.5 months after RTX treatment.Conclusions NMOSD patients carrying the FCGR3A-FF genotype exhibit a higher risk of relapse and shorter time to first relapse after RTX treatment.It is recommended to tailor treatment plans or consider alternative immunosuppressive medications for these individuals.

关 键 词：视神经脊髓炎谱系疾病 利妥昔单抗 Fcγ受体3A 疗效 B细胞 

分 类 号：R744.52[医药卫生—神经病学与精神病学]