PMID- 36389787
OWN - NLM
STAT- MEDLINE
DCOM- 20221121
LR  - 20221122
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Identification of cerebrospinal fluid biomarker candidates for 
      anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic 
      investigation.
PG  - 971659
LID - 10.3389/fimmu.2022.971659 [doi]
LID - 971659
AB  - BACKGROUND: Although the diagnosis is mainly dependent on the detection of 
      anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in cerebrospinal fluid 
      (CSF) and/or serum, there was no direct correlations between anti-NMDAR antibody 
      titers in CSF and disease severity and prognosis in anti-NMDAR encephalitis 
      patients. Here, we aimed to extensively identify CSF biomarkers related to the 
      occurrence, development, and prognosis of anti-NMDAR encephalitis using a 
      high-throughput proteomic approach. METHODS: A CSF cytokine antibody array 
      containing 80 cytokines and inflammatory mediators related to immune and 
      inflammatory responses was applied to identify biomarker candidates in individual 
      CSF samples from a well-characterized cohort comprising patients with anti-NMDAR 
      encephalitis (n = 6) and controls (n = 6). Validation and specific detection were 
      performed in an extended cohort consisting of anti-NMDAR encephalitis patients (n 
      = 13), controls (n = 13), and viral encephalitis (n = 13) by enzyme-linked 
      immunosorbent assay (ELISA). Additionally, the levels of some inflammatory 
      proteins in three groups in cohort 2 reported in previous literatures that may be 
      involved in the development of anti-NMDAR encephalitis were also tested by ELISA. 
      Correlations between candidate biomarkers and clinical characteristics of 
      anti-NMDAR encephalitis patients were analyzed. RESULTS: Three differentially 
      expressed cytokines and inflammatory mediators were screened from the 80-cytokine 
      array in cohort 1. Functional enrichment analysis results suggested that these 
      differentially expressed proteins were related to autophagy, immune/inflammatory 
      responses, cell death, and other processes. In cohort 2, the elevations of 
      cellular inhibitor of apoptosis protein-1 (cIAP-1), macrophage colony-stimulating 
      factor (MCSF), CXC chemokine ligand 13 (CXCL13), and nucleotide binding 
      oligomerization domain-like receptor protein 3 (NLRP3) in anti-NMDAR encephalitis 
      were validated by ELISA. Linear regression revealed that the levels of CSF CXCL13 
      and cIAP-1 were positively correlated with the highest modified Rankin scale 
      (mRS) score in the acute phase (p < 0.05). The level of cIAP-1 was positively 
      correlated with the anti-NMDAR Encephalitis One-Year Functional Status (NEOS) 
      score (p < 0.05). CONCLUSION: These biomarkers show promising functions to 
      evaluate severity or prognosis of anti-NMDAR encephalitis. The biological 
      processes of immune/inflammatory responses, altered levels of autophagy, and the 
      tumor necrosis factor (TNF) signal pathway may be involved in the pathophysiology 
      of anti-NMDAR encephalitis to some extent.
CI  - Copyright (c) 2022 Li, Yang, Zhang, Wang, Shen, Liu, Guo and Wang.
FAU - Li, Yuchen
AU  - Li Y
AD  - Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 
      China.
FAU - Yang, Keyu
AU  - Yang K
AD  - Department of Critical Care Medicine, Aerospace Center Hospital, Beijing, China.
FAU - Zhang, Fang
AU  - Zhang F
AD  - Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 
      China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 
      China.
FAU - Shen, Huijun
AU  - Shen H
AD  - Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 
      China.
FAU - Liu, Miaomiao
AU  - Liu M
AD  - Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 
      China.
FAU - Guo, Junhong
AU  - Guo J
AD  - Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 
      China.
FAU - Wang, Jie
AU  - Wang J
AD  - Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221026
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
SB  - IM
MH  - Humans
MH  - *Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnosis/cerebrospinal fluid
MH  - Proteomics
MH  - Biomarkers
MH  - Cytokines/cerebrospinal fluid
MH  - Inflammation Mediators
PMC - PMC9643472
OTO - NOTNLM
OT  - anti-N-methyl-D-aspartate receptor encephalitis
OT  - biomarkers
OT  - cerebrospinal fluid
OT  - cytokines
OT  - proteomics
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/11/18 06:00
MHDA- 2022/11/22 06:00
PMCR- 2022/01/01
CRDT- 2022/11/17 12:44
PHST- 2022/06/17 00:00 [received]
PHST- 2022/10/03 00:00 [accepted]
PHST- 2022/11/17 12:44 [entrez]
PHST- 2022/11/18 06:00 [pubmed]
PHST- 2022/11/22 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.971659 [doi]
PST - epublish
SO  - Front Immunol. 2022 Oct 26;13:971659. doi: 10.3389/fimmu.2022.971659. eCollection 
      2022.