血清衍生的外泌体 miR-140-5p 作为抗 NMDAR 脑炎与病毒性脑炎鉴别诊断的有前途的生物标志物。
Serum-Derived Exosomal miR-140-5p as a Promising Biomarker for Differential Diagnosis of Anti-NMDAR Encephalitis With Viral Encephalitis.
机构信息
Department of Laboratory Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
出版信息
Front Immunol. 2022 Feb 22;13:840003. doi: 10.3389/fimmu.2022.840003. eCollection 2022.
BACKGROUND
Anti--methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis. Early recognition and treatment, especially distinguishing from viral encephalitis (VE) in the early stages, are crucial for the outcomes of patients with anti-NMDAR encephalitis. Compared with plasma microRNAs (miRNAs), exosomal miRNAs are more abundant and not easy to degrade. Moreover, exosomes can pass through the blood-brain barrier. This study aimed to explore the clinical value of serum exosomal miRNAs in the differential diagnosis of anti-NMDAR encephalitis with VE.
METHOD
Serum samples from a total of 30 patients with anti-NMDAR encephalitis, 30 patients with VE, and 30 cases of control patients hospitalized in the same period were collected. Firstly, the serum exosomes were isolated and identified by transmission electron microscope (TEM), nanoparticle-tracking analyzer (NTA), and Western blot (WB). The expression levels of let-7b and miR-140-5p from serum exosomes were detected by real-time quantitative PCR (qPCR). At the same time, we also detected complement 3 (C3), complement 4 (C4), and high sensitivity CRP (hs-CRP) expression levels in three groups. Finally, we analyzed the difference and diagnostic value of the test results.
RESULTS
Isolated particles showed identical characteristics to the exosomes through TEM, NTA, and WB analyses. Compared with the VE group and control group, the expression of miR-140-5p was significantly upregulated in serum exosomes of the NMDAR group. In contrast, the serum C3 in the NMDAR group was significantly lower than the other two groups. ROC curve analysis showed the area under the curve (AUC) of serum exosomal miR-140-5p and serum C3 was 0.748 (76.67% sensitivity and 73.33% specificity) and 0.724 (76.67% sensitivity and 60% specificity) to distinguish anti-NMDAR encephalitis from VE, respectively. The AUC of serum exosomal miR-140-5p combined with serum C3 was 0.811, the sensitivity was 70.00%, and the specificity was 86.67%.
CONCLUSION
Serum exosomal miR-140-5p combined with serum C3 would be a promising marker in the differential diagnosis of anti-NMDAR encephalitis with VE.
背景
抗 N-甲基-D-天冬氨酸受体（anti-NMDAR）脑炎是最常见的自身免疫性脑炎类型。早期识别和治疗，特别是在早期与病毒性脑炎（VE）相鉴别，对抗 NMDAR 脑炎患者的预后至关重要。与血浆 microRNAs（miRNAs）相比，外泌体 miRNAs 更为丰富且不易降解。此外，外泌体可以穿过血脑屏障。本研究旨在探讨血清外泌体 miRNAs 在鉴别诊断抗 NMDAR 脑炎与 VE 中的临床价值。
方法
收集了 30 例抗 NMDAR 脑炎患者、30 例 VE 患者和 30 例同期住院的对照患者的血清样本。首先，通过透射电子显微镜（TEM）、纳米颗粒跟踪分析仪（NTA）和 Western blot（WB）鉴定血清外泌体。采用实时定量 PCR（qPCR）检测血清外泌体中 let-7b 和 miR-140-5p 的表达水平。同时，我们还检测了三组中补体 3（C3）、补体 4（C4）和高敏 C 反应蛋白（hs-CRP）的表达水平。最后，我们分析了检测结果的差异和诊断价值。
结果
通过 TEM、NTA 和 WB 分析，分离出的颗粒与外泌体具有相同的特征。与 VE 组和对照组相比，NMDAR 组血清外泌体中 miR-140-5p 的表达明显上调。相反，NMDAR 组血清 C3 明显低于另外两组。ROC 曲线分析显示，血清外泌体 miR-140-5p 和血清 C3 的 AUC 分别为 0.748（76.67%的灵敏度和 73.33%的特异性）和 0.724（76.67%的灵敏度和 60%的特异性），用于区分抗 NMDAR 脑炎与 VE。血清外泌体 miR-140-5p 联合血清 C3 的 AUC 为 0.811，灵敏度为 70.00%，特异性为 86.67%。
结论
血清外泌体 miR-140-5p 联合血清 C3 可能成为鉴别抗 NMDAR 脑炎与 VE 的有前途的标志物。
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