外周血 BAFF、HMGB1、miR-219a-5p 在小儿癫痫中的表达水平及临床意义

The expression levels and clinical significance of BAFF, HMGB1 and miR-219a-5p in peripheral blood of children with epilepsy

摘要

目的: 探讨 B 细胞活化因子(B-cell activating factor of TNF family,BAFF)、高迁移率族蛋白 B1(high-mobility group box-1,HMGB1)、miR-219a-5p 在癫痫患儿外周血中的表达水平及预后评估价值。 方法: 选取 2023 年 4 月至 2024 年 3 月青岛市市立医院收治的 84 例癫痫患儿为癫痫组,同期 84 例健康体检儿童为对照组;依据格拉斯哥预后评分将癫痫组分为预后良好组(n = 61) 和预后不良组(n = 23)。 收集所有研究对象基线资料,分别采用 ELISA 法、流式荧光法、qRT-PCR 检测外周血 BAFF、HMGB1、miR-219a-5p 表达水平;对比两组及不同预后亚组临床指标与分子表达差异;采用多因素 Logistic 回归分析癫痫预后不良独立危险因素;Spearman 相关分析三种分子指标间的相关性;ROC 曲线分析三项指标联合预测不良预后的效能。 结果: 癫痫组外周血 BAFF、HMGB1、miR-219a-5p 表达水平均显著高于对照组(P<0.01);预后不良组患儿治疗前发作频率、发作持续时间及三项分子指标水平均高于预后良好组( P 均< 0.01)。Logistic 回归结果显示,治疗前发作频率过高、发作持续时间延长、外周高表达 BAFF、HMGB1、miR-219a-5p 均为小儿癫痫预后不良独立危险因素( P< 0.05)。Spearman 相关分析结果提示,BAFF、HMGB1、miR-219a-5p 两两呈正相关(r 值分别为 0.468、0.432、0.547,P<0.05)。ROC 曲线分析结果显示,三项指标联合检测的曲线下面积为 0.851,敏感度为 0.87,特异度为 0.81,预测效能最优(P<0.05)。 结论: BAFF、HMGB1、miR-219a-5p 在小儿癫痫患儿外周血中呈高表达,均为预后不良独立危险因素;三项指标联合检测可显著提升对小儿癫痫不良预后的预测效能。

Abstract

Objective: To investigate the expression levels and prognostic value of peripheral blood B-cell activating factor of TNF family (BAFF), high-mobility group box-1 (HMGB1) and miR-219a-5p in children with epilepsy. Methods: A total of 84 children with epilepsy admitted to Qingdao Municipal Hospital from April 2023 to March 2024 were selected as the epilepsy group, and 84 healthy children receiving physical examinations during the same period were set as the control group. According to the Glasgow Outcome Scale, the epilepsy group was subdivided into a good prognosis subgroup (n = 61) and a poor prognosis subgroup (n = 23). Baseline data of all subjects were collected. The expression levels of peripheral blood BAFF, HMGB1 and miR-219a-5p were detected by ELISA, fluorescence flow cytometry and qRT-PCR, respectively. The differences in clinical indicators and molecular expression were compared between the two groups and different prognosis subgroups. Multivariate Logistic regression analysis was performed to screen independent risk factors for poor epilepsy prognosis. Spearman correlation analysis was used to analyze the correlations among the three molecular markers, and receiver operating characteristic (ROC) curves were plotted to evaluate the efficacy of combined detection of the three indicators in predicting poor prognosis. Results: The expression levels of BAFF, HMGB1 and miR-219a-5p in the epilepsy group were significantly higher than those in the control group (P<0.01). The pre-treatment seizure frequency, seizure duration and levels of the three molecular markers in the poor prognosis subgroup were all higher than those in the good prognosis subgroup (all P<0.01). Logistic regression analysis showed that high pre-treatment seizure frequency, prolonged seizure duration and overexpression of peripheral BAFF, HMGB1 and miR-219a-5p were independent risk factors for poor prognosis of pediatric epilepsy (P<0.05). Spearman analysis indicated that BAFF, HMGB1 and miR-219a-5p were positively correlated with each other, with correlation coefficients r of 0.468, 0.432 and 0.547, respectively (P< 0.05). ROC curve analysis revealed that the area under the curve of the combined three indicators was 0.851, with a sensitivity of 0.87 and a specificity of 0.81, and the predictive efficacy was superior to that of single marker detection (P< 0.05). Conclusion: BAFF, HMGB1 and miR-219a-5p are highly expressed in the peripheral blood of children with epilepsy, and all may serve as independent risk factors for poor prognosis. Combined detection of the three indicators can significantly improve the predictive efficiency of adverse prognosis in pediatric epilepsy.

关键词

小儿癫痫 / 外周血 B 细胞活化因子 / 高迁移率族蛋白 B1 / miR-219a-5p / 诊断效能

Key words

pediatric epilepsy / B-cell activating factor of TNF family / high-mobility group box-1 / miR-219a-5p / diagnostic effectiveness

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基金资助

青岛市市南区科技发展资金项目(2018-4-023-YY)