Btk/NF-κB信号通路在视神经脊髓炎谱系疾病中变化及意义

Changes and significance of Btk/NF-κB signaling pathway in neuromyelitis optic spectrum disease

目的检测NMOSD急性期患者单个核细胞(PBMCs)的BTK/NF-κB信号通路中BTK、NF-κB、PI3K、IKK mRNA水平,探讨BTK、NF-κB、PI3K、IKK在NMOSD患者急性期变化及可能作用;探讨NMOSD患者血清AQP4-Ab阳性与否、抗体水平与脊髓MRI受累节段数的相关性。方法选取2018年1月-2019年1月就诊于河北医科大学第二医院神经内科NMOSD急性期患者33例为实验组,性别、年龄相匹配的33例健康人为对照组。入组的NMOSD患者进行EDSS评分、脊髓MRI检查、血AQP4-Ab测定。留取外周血,分离PBMCs,采用RT-PCR法检测PBMCs中BTK、NF-κB、PI3K、IKK水平,将其与健康人比较。结果 NMOSD组BTK/NF-κB信号通路中Btk、NF-κB、PI3K、IKK mRNA水平均较对照组明显升高,差异有统计学意义;NMOSD急性期患者AQP4-Ab阳性者较AQP4-Ab阴性者脊髓受累节段数多,差异有统计学意义;AQP4-Ab抗体滴度与脊髓受累节段数无线性相关关系。结论BTK/NF-κB信号通路中4项激酶在NMOSD急性期增高,在调控B细胞分化时异常激活,可能参与了疾病发生;NMOSD患者急性期脊髓受累节段数可能与血AQP4-Ab阳性相关,滴度并不能预测脊髓受累节段数。

Objective The mRNA levels of BTK,NF-κB,PI3 K,and IKK in the BTK/NF-κB signaling pathway of PBMCs in NMOSD patients were detected,and the changes and possible roles of BTK,NF-kappa B,PI3 K,and IKK in NMOSD patients in the acute stage were discussed. To investigate the correlation between serum AQP4-Ab positivity,antibody level and the number of involved segments in spinal cord MRI in NMOSD patients. Methods From January 2018 to January 2019,33 patients admitted to the department of neurology of the Second Hospital of Hebei Medical University in the acute phase of NMOSD were selected as the experimental group,and 33 healthy patients with matching gender and age were selected as the control group. EDSS score,spinal cord MRI and blood AQP4-Ab were measured in the enrolled NMOSD patients. The levels of BTK,NF-κB,PI3 K and IKK in PBMCs were detected by PCR,and compared with those in healthy subjects. Results The levels of BTK,NF-κB,PI3 K,IKK mRNA in the NMOSD group were significantly higher than those in the control group. Compared with AQP4-Ab negative patients,AQP4-Ab positive patients in the acute phase of NMOSD had more spinal cord involvement segments,and the difference was statistically significant. There was no linear correlation between the titer of AQP4-Ab antibody and the number of spinal cord involved segments. Conclusion The BTK/NF-κB signaling pathway may be involved in the pathogenesis of NMOSD,as its abnormal increase may interfere with the proliferation and differentiation of B cell. The number of spinal cord involved segments in the acute phase of NMOSD patients may be correlated with positive blood AQP4-Ab,and the titer does not predict the number of spinal cord involved segments.