Exosomal miR-432-5p, miR-4433b-5p, and miR-599: Biomarkers for Monitoring the Severity of Anti-N-methyl-D-aspartate Receptor Encephalitis

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare disease with a high disability rate, characterized by acute-to-subacute psychiatric and/or neurological symptoms. Continuous intrathecal antibody synthesis does not correlate with the active phase of enc...

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Main Authors: Zhuxiao Xie, Lei Liu, Yanjun Guo, Hanqiu Jiang, Lin Li, Zhixin Qiao, Jiawei Wang
Format: Article
Language:English
Published: IMR Press 2025-05-01
Series:Journal of Integrative Neuroscience
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Online Access:https://www.imrpress.com/journal/JIN/24/5/10.31083/JIN37513
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author Zhuxiao Xie
Lei Liu
Yanjun Guo
Hanqiu Jiang
Lin Li
Zhixin Qiao
Jiawei Wang
author_facet Zhuxiao Xie
Lei Liu
Yanjun Guo
Hanqiu Jiang
Lin Li
Zhixin Qiao
Jiawei Wang
author_sort Zhuxiao Xie
collection DOAJ
description Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare disease with a high disability rate, characterized by acute-to-subacute psychiatric and/or neurological symptoms. Continuous intrathecal antibody synthesis does not correlate with the active phase of encephalitis and antibody titers do not directly reflect the severity of the condition. Currently, there is a lack of biomarkers for disease monitoring. This study focuses on finding novel peripheral blood biomarkers that can accurately monitor the severity of anti-NMDAR encephalitis. Methods: Peripheral blood samples were collected from patients with anti-NMDAR encephalitis, including those with acute-phase (autoimmune encephalitis (AE)-a group) and stable-phase (AE-s group) autoimmune encephalitis. Healthy individuals were included as controls (HC group). We isolated exosomal microRNAs (miRNAs) from the samples and screened differentially expressed miRNAs through next-generation sequencing. The sequencing results were validated using quantitative real-time qPCR (RT-qPCR). Furthermore, we conducted a correlation analysis between the expression levels of the screened miRNAs and clinical severity. Finally, we performed functional pathway analysis to explore the underlying mechanisms in anti-NMDAR encephalitis. Results: We found that exosomal miR-432-5p, miR-4433b-5p, and miR-599 exhibited significant differences between patients with anti-NMDAR encephalitis and healthy controls, as well as at various phases of the disease. The expression of miR-432-5p and miR-4433b-5p were negatively correlated with clinical severity. We further identified that key pathways including rhythmic processes and glutamatergic signaling play significant roles in the pathogenesis of anti-NMDAR encephalitis. Conclusions: Our research indicated that exosomal miR-432-5p, miR-4433b-5p, and miR-599 were correlated with the severity of anti-NMDAR encephalitis and can serve as potential biomarkers for disease monitoring. Moreover, the key functional pathways predicted by these miRNAs may play crucial roles in disease progression.
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spelling doaj-art-56387a3b3bd44b57801fa9ccd7cb15232025-08-20T03:25:59ZengIMR PressJournal of Integrative Neuroscience0219-63522025-05-012453751310.31083/JIN37513S0219-6352(25)00947-7Exosomal miR-432-5p, miR-4433b-5p, and miR-599: Biomarkers for Monitoring the Severity of Anti-N-methyl-D-aspartate Receptor EncephalitisZhuxiao Xie0Lei Liu1Yanjun Guo2Hanqiu Jiang3Lin Li4Zhixin Qiao5Jiawei Wang6Department of Neurology, Beijing Tongren Hospital, Capital Medical University, 100000 Beijing, ChinaDepartment of Neurology, Beijing Tongren Hospital, Capital Medical University, 100000 Beijing, ChinaDepartment of Neurology, Beijing Tongren Hospital, Capital Medical University, 100000 Beijing, ChinaDepartment of Neurology, Beijing Tongren Hospital, Capital Medical University, 100000 Beijing, ChinaDepartment of Neurology, Beijing Tongren Hospital, Capital Medical University, 100000 Beijing, ChinaClinical Research Center, Beijing Tongren Hospital, Capital Medical University, 100000 Beijing, ChinaDepartment of Neurology, Beijing Tongren Hospital, Capital Medical University, 100000 Beijing, ChinaBackground: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare disease with a high disability rate, characterized by acute-to-subacute psychiatric and/or neurological symptoms. Continuous intrathecal antibody synthesis does not correlate with the active phase of encephalitis and antibody titers do not directly reflect the severity of the condition. Currently, there is a lack of biomarkers for disease monitoring. This study focuses on finding novel peripheral blood biomarkers that can accurately monitor the severity of anti-NMDAR encephalitis. Methods: Peripheral blood samples were collected from patients with anti-NMDAR encephalitis, including those with acute-phase (autoimmune encephalitis (AE)-a group) and stable-phase (AE-s group) autoimmune encephalitis. Healthy individuals were included as controls (HC group). We isolated exosomal microRNAs (miRNAs) from the samples and screened differentially expressed miRNAs through next-generation sequencing. The sequencing results were validated using quantitative real-time qPCR (RT-qPCR). Furthermore, we conducted a correlation analysis between the expression levels of the screened miRNAs and clinical severity. Finally, we performed functional pathway analysis to explore the underlying mechanisms in anti-NMDAR encephalitis. Results: We found that exosomal miR-432-5p, miR-4433b-5p, and miR-599 exhibited significant differences between patients with anti-NMDAR encephalitis and healthy controls, as well as at various phases of the disease. The expression of miR-432-5p and miR-4433b-5p were negatively correlated with clinical severity. We further identified that key pathways including rhythmic processes and glutamatergic signaling play significant roles in the pathogenesis of anti-NMDAR encephalitis. Conclusions: Our research indicated that exosomal miR-432-5p, miR-4433b-5p, and miR-599 were correlated with the severity of anti-NMDAR encephalitis and can serve as potential biomarkers for disease monitoring. Moreover, the key functional pathways predicted by these miRNAs may play crucial roles in disease progression.https://www.imrpress.com/journal/JIN/24/5/10.31083/JIN37513anti-n-methyl-d-aspartate receptor encephalitisexosomesmonitormir-432-5pmir-4433b-5pmir-599
spellingShingle Zhuxiao Xie
Lei Liu
Yanjun Guo
Hanqiu Jiang
Lin Li
Zhixin Qiao
Jiawei Wang
Exosomal miR-432-5p, miR-4433b-5p, and miR-599: Biomarkers for Monitoring the Severity of Anti-N-methyl-D-aspartate Receptor Encephalitis
Journal of Integrative Neuroscience
anti-n-methyl-d-aspartate receptor encephalitis
exosomes
monitor
mir-432-5p
mir-4433b-5p
mir-599
title Exosomal miR-432-5p, miR-4433b-5p, and miR-599: Biomarkers for Monitoring the Severity of Anti-N-methyl-D-aspartate Receptor Encephalitis
title_full Exosomal miR-432-5p, miR-4433b-5p, and miR-599: Biomarkers for Monitoring the Severity of Anti-N-methyl-D-aspartate Receptor Encephalitis
title_fullStr Exosomal miR-432-5p, miR-4433b-5p, and miR-599: Biomarkers for Monitoring the Severity of Anti-N-methyl-D-aspartate Receptor Encephalitis
title_full_unstemmed Exosomal miR-432-5p, miR-4433b-5p, and miR-599: Biomarkers for Monitoring the Severity of Anti-N-methyl-D-aspartate Receptor Encephalitis
title_short Exosomal miR-432-5p, miR-4433b-5p, and miR-599: Biomarkers for Monitoring the Severity of Anti-N-methyl-D-aspartate Receptor Encephalitis
title_sort exosomal mir 432 5p mir 4433b 5p and mir 599 biomarkers for monitoring the severity of anti n methyl d aspartate receptor encephalitis
topic anti-n-methyl-d-aspartate receptor encephalitis
exosomes
monitor
mir-432-5p
mir-4433b-5p
mir-599
url https://www.imrpress.com/journal/JIN/24/5/10.31083/JIN37513
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