Liu Jing, Wang Gaoning, Shi Mengya, Guo Ruo-Yi, Yuan Congcong, Wang Yulin, Mehmood Arshad, Zhang Lu, Li Bin
Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
The Key Laboratory of Neurology, Shijiazhuang, 050000, Hebei, China.
Mol Neurobiol. 2025 Apr;62(4):4785-4801. doi: 10.1007/s12035-024-04588-5. Epub 2024 Nov 1.
This study investigated the potential correlation between BTK/YKL-40 levels and the severity of AQP4-IgG + NMOSD, aiming to identify biomarkers for disease monitoring and treatment assessment. Plasma YKL-40 expression was measured in 135 AQP4-IgG + NMOSD patients using ELISA. Patients were categorized into pre- and post-IVMP treatment acute phases, as well as during remission, with a healthy control group included. BTK and NF-κB mRNA levels in PBMCs were detected via q-PCR, and BTK/P-BTK protein expression was assessed using Western blotting. Disability was evaluated using the EDSS score, and clinical characteristics were evaluated alongside laboratory tests. Acute-phase NMOSD patients receiving pre-IVMP therapy presented significantly elevated plasma YKL-40 concentrations compared with those of post-treatment patients, patients in remission, and healthy controls. Additionally, these patients presented significantly higher levels of PBMC BTK mRNA, NF-κB mRNA, BTK, and P-BTK protein expression than remission patients and healthy controls. Plasma YKL-40 levels and PBMC BTK/P-BTK protein levels were positively correlated with EDSS scores. The plasma YKL-40 concentration significantly contributes to disease severity and serves as an independent risk factor for acute NMOSD. Elevated BTK, P-BTK, NF-κB, and YKL-40 levels were observed in acute-phase AQP4-IgG + NMOSD patients. These biomarkers are related to disease activity and may predict treatment efficacy. There is a connection among YKL-40, BTK, and P-BTK levels and disease severity, suggesting their potential involvement in the pathogenic mechanism of AQP4-IgG + NMOSD.
本研究调查了BTK/YKL-40水平与水通道蛋白4抗体阳性视神经脊髓炎谱系疾病（AQP4-IgG+NMOSD）严重程度之间的潜在相关性，旨在确定用于疾病监测和治疗评估的生物标志物。采用酶联免疫吸附测定（ELISA）法检测了135例AQP4-IgG+NMOSD患者血浆中YKL-40的表达。患者被分为静脉注射甲泼尼龙（IVMP）治疗前和治疗后的急性期以及缓解期，并纳入一个健康对照组。通过定量聚合酶链反应（q-PCR）检测外周血单个核细胞（PBMCs）中BTK和核因子κB（NF-κB）的mRNA水平，并用蛋白质免疫印迹法评估BTK/P-BTK蛋白表达。使用扩展残疾状态量表（EDSS）评分评估残疾情况，并结合实验室检查评估临床特征。与治疗后患者、缓解期患者和健康对照组相比，接受IVMP治疗前的急性期NMOSD患者血浆YKL-40浓度显著升高。此外，这些患者的PBMCs中BTK mRNA、NF-κB mRNA、BTK和P-BTK蛋白表达水平明显高于缓解期患者和健康对照组。血浆YKL-40水平和PBMCs中BTK/P-BTK蛋白水平与EDSS评分呈正相关。血浆YKL-40浓度对疾病严重程度有显著影响，是急性NMOSD的独立危险因素。在急性期AQP4-IgG+NMOSD患者中观察到BTK、P-BTK、NF-κB和YKL-40水平升高。这些生物标志物与疾病活动相关，可能预测治疗效果。YKL-40、BTK和P-BTK水平与疾病严重程度之间存在关联，提示它们可能参与AQP4-IgG+NMOSD的致病机制。
