Evidence map›Paper›PMID 42018084›Full record

ArticleJournal of clinical immunology2026

Translating Host-Derived Signals from Cerebrospinal Fluid Metagenomic Sequencing into a Diagnostic Tool for Autoimmune Encephalitis in Children.

Dingding Han, Xiaozhou Pan, Fen Pan, Biyun Han, Qianyue Wu, Yiping Zhou, Huifang Liu, Huan Xu, Weifen Sun, Hongyi Cheng and 4 more

Abstract read
In one paragraph

Article in Journal of clinical immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Dingding Han *Department of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China. handingding517@hotmail.com.ORCID http://orcid.org/0000-0003-0963-6286
Xiaozhou Pan *Department of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Fen PanDepartment of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Biyun HanDepartment of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Qianyue WuDepartment of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Yiping ZhouDepartment of Critical Care Medicine, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
Huifang LiuVision Medicals Co. Ltd, Guangzhou, 510663, China.
Huan XuVision Medicals Co. Ltd, Guangzhou, 510663, China.
Weifen SunShanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of Justice, Shanghai, 200063, China.
Hongyi ChengDepartment of Neurology, Shanghai Children's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, 200062, China.
Wenxin LiuDepartment of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Rujia WanDepartment of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Wenhao WengDepartment of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China. Wengwenhao@shchildren.com.cn.
Hong ZhangDepartment of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China. schjyk2015@126.com.

Funding

National Natural Science Foundation of China 82471882Natural Science Foundation of Shanghai Municipality 21ZR1452900Shanghai Municipal Key Specialty shslczdzk06902Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai (2023-2025) GWVI-3
6 · The paper itself

Abstract

backgroundThe rapid differentiation between autoimmune and infectious encephalitis in children is a critical clinical decision that dramatically impacts treatment and outcome. Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is a powerful but often underutilized tool, as its host-derived RNA component is typically discarded. We hypothesized that this host response data could be translated into a diagnostic tool for autoimmune encephalitis (AE).

methodsWe enrolled 180 pediatric patients with suspected encephalitis to evaluate the clinical performance of CSF mNGS against conventional methods. Host transcriptomic analysis was performed on CSF cells from 88 patients (autoimmune, bacterial, and viral encephalitis). A novel biomarker was validated using RT-qPCR in an independent cohort, and its functional role was investigated in neuronal cultures challenged with NMDAR1 antibodies. A diagnostic model was developed and validated.

resultsmNGS demonstrated a significantly higher pathogen detection rate than conventional methods (29.4% vs. 16.7%). Host transcriptomic profiling revealed that AE shared a hyperinflammatory signature with viral encephalitis but was uniquely associated with dysregulation of receptor tyrosine kinase and heme signaling pathways. Furthermore, memory B cells and activated mast cells were specifically elevated in AE. We identified and validated RAD54B as a novel biomarker specifically upregulated in AE. Functionally, RAD54B upregulation protected neurons from DNA damage stress induced by NMDAR1 antibodies. A multi-gene diagnostic model based on host-response genes robustly differentiated AE from infectious encephalitis (AUC > 0.923) in a validation set.

conclusionsWe present a validated translational pipeline that repurposes routine CSF mNGS data into a dual-purpose diagnostic tool. By leveraging the host RNA data inherent in CSF mNGS, clinicians can now simultaneously investigate infectious and autoimmune etiologies in a single, rapid test. This strategy has the immediate potential to reduce diagnostic delay, guide timely therapy, and improve outcomes in children with encephalitis.

Indexed as

EncephalitisHashimoto DiseaseMetagenomicsAdolescentBiomarkersChildChild, PreschoolFemaleGene Expression ProfilingHigh-Throughput Nucleotide SequencingHumansInfantMaleReceptors, N-Methyl-D-AspartateTranscriptomeBiomarkersReceptors, N-Methyl-D-AspartateAutoimmune encephalitisBiomarkerDiagnostic modelHost transcriptomeMetagenomic next-generation sequencing (mNGS)Pediatric encephalitis

Identifiers

PMID42018084
PMCPMC13236776

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.