【摘要】 目的 探索重症肌无力(MG)患者血清总白细胞介素-18(IL-18)、IL-18结合蛋白(IL-18BP)、游离IL-18(fIL-18)表达的变化及其临床意义。方法 收集2021年9月至2024年1月苏州大学附属第一医院神经内科收治的MG患者122例，其中男56例，女66例，年龄(48.9±15.2)岁，病程中位数(四分位数)为12.00(4.00,36.00)个月；另招募作者医院体检中心与MG患者性别构成、年龄、民族相匹配的42名健康志愿者作为健康对照。采用酶联免疫吸附测定法(ELISA)测定受试者血清总IL-18、IL-18BP和fIL-18水平，比较MG患者与健康对照组以及不同临床特征MG亚组间总IL-18、IL-18BP、IL-18/IL-18BP比值和fIL-18水平的差异，并分析IL-18相关指标与定量MG评分(QMGs)和乙酰胆碱受体抗体(AChR-Ab)的相关性。结果 基线期MG外周血总IL-18、IL-18/IL-18BP、fIL-18均高于健康对照(P<0.05),且基线期和复发期MG患者这些指标均高于缓解期(P<0.05);基线期MG患者总IL-18(r=0.556,P<0.01)、IL-18BP(r=0.407,P<0.05)、IL-18/IL-18BP(r=0.434,P<0.01)和fIL-18(r=0.616,P<0.01)与QMGs呈正相关；全身型MG患者总IL-18、fIL-18高于眼肌型患者(P<0.05);复发期MG患者总IL-18(r=0.502,P<0.01)、IL-18BP(r=0.575,P<0.01)水平与QMGs呈正相关，且IL-18BP与AChR-Ab滴度呈正相关(r=0.380,P<0.05)。14例基线期MG患者经免疫抑制剂治疗后总IL-18、fIL-18水平和QMGs均较治疗前下降(P<0.05)。结论 IL-18和IL-18BP水平失衡可能参与了MG的病理生理过程，这种失衡可能和IL-18BP相对分泌不足有关。靶向IL-18治疗可能成为一个潜在的治疗策略。更多还原

【Abstract】 Objective To explore the changes and expression of total interleukin-18(IL-18), IL-18 binding protein(IL-18BP), IL-18/IL-18BP ratio and free IL-18(fIL-18) in myasthenia gravis(MG).Methods A total of 122 patients with MG admitted to the Neurology Department of the First Affiliated Hospital of Soochow University from September 2021 to January 2024 were collected, including 56 males and 66 females, with an average age of(48.9±15.2) years and a median disease duration(quartiles) of 12.00(4.00, 36.00) months. In addition, 42 healthy volunteers who matched the gender composition, age, and ethnicity of MG patients were recruited from the authors’ hospital physical examination center. Enzyme-linked immunosorbent assay(ELISA) was used to determine serum total IL-18, IL-18BP and fIL-18 levels in the subjects. The differences in total IL-18, IL-18BP, IL-18/IL-18BP ratio and fIL-18 levels between MG patients and healthy controls, and between MG subgroups were compared. We also analyzed the correlation between IL-18-related indices, quantitative MG scores(QMGs) and acetylcholine receptor antibody(AChR-Ab).Results Total IL-18, IL-18/IL-18BP, and fIL-18 in peripheral blood were higher in the patients with MG at baseline than those in healthy controls(P<0.05), and these indices were higher in both baseline and relapse than those in remission(P<0.05). Total IL-18(r=0.556, P<0.01), IL-18BP(r=0.407, P<0.05), IL-18/IL-18BP(r=0.434, P<0.01), and fIL-18(r=0.616, P<0.01) were positively correlated with QMGs in the patients with MG in baseline phase. Total IL-18 and fIL-18 were higher in patients with generalized MG than in those with ocular MG(P<0.05). Total IL-18(r=0.502, P<0.01) and IL-18BP(r=0.575, P<0.01) were positively correlated with QMGs in MG patients in relapse phase, and IL-18BP was positively correlated with AChR-Ab titer(r=0.380, P<0.05). Total IL-18, fIL-18 and QMGs decreased after immunosuppressive treatment compared with pretreatment in 14 MG patients in baseline phase(P<0.05).Conclusions Imbalance of IL-18 and IL-18BP levels may be involved in the pathophysiological process of MG, and this imbalance may be related to the relative underproduction of IL-18BP. Targeting IL-18 therapy could be a potential therapeutic strategy that deserves further investigation.更多还原