PMID- 36224320 OWN - NLM STAT- MEDLINE DCOM- 20221228 LR - 20221228 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 60 IP - 1 DP - 2023 Jan TI - Multi-proteomic Analysis Revealed Distinct Protein Profiles in Cerebrospinal Fluid of Patients Between Anti-NMDAR Encephalitis NORSE and Cryptogenic NORSE. PG - 98-115 LID - 10.1007/s12035-022-03011-1 [doi] AB - New-onset refractory status epilepticus (NORSE) is rare but intractable. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and cryptogenic etiologies are the two major causes of NORSE with distinct clinical features. To elucidate the underlying mechanisms, 6 patients with anti-NMDAR encephalitis NORSE and 5 with cryptogenic NORSE (C-NORSE) were enrolled. Five patients of cerebrovascular disorders were used as controls. Quantitative proteomic analysis of the cerebrospinal fluid (CSF) samples of the patients revealed 101 and 56 proteins were changed, respectively. The average fold-change of the upregulated proteins, namely up-proteomic score in this study, was positively correlated with the severity and prognosis of the diseases, including ICU stay (r = 0.9308, P = 0.0035 in NMDAR group; r = 0.8977, P = 0.0193 in C-NORSE group), mRS score at discharge (r = 0.9710, P = 0.0111 in NMDAR group; r = 0.7071, P = 0.2000 in C-NORSE group), and time taken for patients awaking from a coma (r = 0.8823, P = 0.0100 in NMDAR group; r = 0.7906, P = 0.2000 in C-NORSE group). Pathways involved in humoral immune response, wound healing, and epigenetic regulation of transcription were upregulated in anti-NMDAR encephalitis NORSE. Pathways of innate and lymphocyte mediated immune response, synaptic functions, ubiquitination, and cell apoptosis were up-regulated in C-NORSE, which was consistent with a mouse model of status epilepticus. Fc receptor and B cell mediated immunity signaling pathways were downregulated in C-NORSE. Immunome microarray analysis demonstrated high autoantibody targeting 48 proteins in CSF samples of anti-NMDAR encephalitis NORSE. While the reaction was kept at a very low level in C-NORSE. There is no significant difference in inflammatory cytokine level between each group. The level of IL-4 (r = 0.7435, P = 0.0451), IL-13 (r = 0.7643, P = 0.0384), IFN-gamma (r = 0.7973, P = 0.0287) and TNF-alpha (r = 0.8598, P = 0.0141) in NMDAR group, and IL-6 (r = 0.8479, P = 0.0348), IL-8 (r = 0.9076, P = 0.0166) in C-NORSE group were positively correlated with the up-proteomic score. The present study suggests that the up-proteomic score of CSF could be a promising indicator for assessment of the severity of anti-NMDAR encephalitis NORSE and C-NORSE. The distinct CSF proteomes imply different pathogenic mechanisms of the two diseases, and immunotherapy strategies as well. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Wang, Dongmei AU - Wang D AD - Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. FAU - Wu, Yongming AU - Wu Y AD - Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. FAU - Pan, Yue AU - Pan Y AD - Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. FAU - Wang, Shengnan AU - Wang S AD - Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. FAU - Liu, Guanghui AU - Liu G AD - Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. FAU - Gao, Yibo AU - Gao Y AD - Central Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, China. gaoyibo@cicams.ac.cn. AD - Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. gaoyibo@cicams.ac.cn. AD - Laboratory of Translational Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. gaoyibo@cicams.ac.cn. AD - State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. gaoyibo@cicams.ac.cn. FAU - Xu, Kaibiao AU - Xu K AUID- ORCID: 0000-0001-8278-6438 AD - Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. xukaibiao@163.com. LA - eng GR - 82171602/National Natural Science Foundation of China/ GR - 82071484/National Natural Science Foundation of China/ GR - 2019B007/President Foundation of Nanfang Hospital/ GR - 2020B008/President Foundation of Nanfang Hospital/ GR - A2021151/Medical Science and Technology Foundation of Guangdong Province/ GR - 2019A1515011760/Natural Science Foundation of Guangdong Province/ PT - Journal Article DEP - 20221012 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Cytokines) RN - 0 (Receptors, N-Methyl-D-Aspartate) SB - IM MH - Animals MH - Mice MH - *Anti-N-Methyl-D-Aspartate Receptor Encephalitis/cerebrospinal fluid MH - Cytokines/cerebrospinal fluid MH - Epigenesis, Genetic MH - Proteomics MH - Receptors, N-Methyl-D-Aspartate MH - *Status Epilepticus/drug therapy MH - Humans OTO - NOTNLM OT - Anti-NMDAR encephalitis OT - Cerebrospinal fluid proteome OT - Cryptogenic-NORSE OT - Immune response OT - Neurodegeneration OT - Status epilepticus EDAT- 2022/10/13 06:00 MHDA- 2022/12/21 06:00 CRDT- 2022/10/12 23:27 PHST- 2022/05/09 00:00 [received] PHST- 2022/08/21 00:00 [accepted] PHST- 2022/10/13 06:00 [pubmed] PHST- 2022/12/21 06:00 [medline] PHST- 2022/10/12 23:27 [entrez] AID - 10.1007/s12035-022-03011-1 [pii] AID - 10.1007/s12035-022-03011-1 [doi] PST - ppublish SO - Mol Neurobiol. 2023 Jan;60(1):98-115. doi: 10.1007/s12035-022-03011-1. Epub 2022 Oct 12.