Brain molecular mechanisms in Rasmussen encephalitis.
RNAseq
Rasmussen encephalitis
exome
proteomics
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
revised:
02
11
2022
received:
16
06
2022
accepted:
03
11
2022
pmc-release:
01
01
2024
pubmed:
8
11
2022
medline:
21
1
2023
entrez:
7
11
2022
Statut:
ppublish
Résumé
This study was undertaken to identify molecular mechanisms in brain tissue of Rasmussen encephalitis (RE) when compared to people with non-RE epilepsy (PWE) and control cases using whole exome sequencing (WES), RNAseq, and proteomics. Frozen brain tissue (ages = 2-19 years) was obtained from control autopsy (n = 14), surgical PWE (n = 10), and surgical RE cases (n = 27). We evaluated WES variants in RE associated with epilepsy, seizures, RE, and human leukocyte antigens (HLAs). Differential expression was evaluated by RNAseq (adjusted p < .05) and label-free quantitative mass spectrometry (false discovery rate < 5%) in the three groups. WES revealed no common pathogenic variants in RE, but several rare and likely deleterious variants of unknown significance (VUS; ANGPTL7/MTOR, SCN1A, FCGR3B, MTOR) and more common HLA VUS in >25% of RE cases (HLA-DRB1, HLA-DQA2), all with allele frequency < 5% in the general population. RNAseq in RE versus PWE (1516 altered transcripts) revealed significant activation of crosstalk between dendritic and natural killer cells (p = 7.94 × 10 In RE, we identified activated immune signaling pathways and immune cell type annotation enrichment that suggest roles of the innate and adaptive immune responses, as well as HLA variants that may increase vulnerability to RE. Follow-up studies could evaluate cell type density and subregional localization associated with top targets, clinical history (neuropathology, disease duration), and whether modulating crosstalk between dendritic and natural killer cells may limit disease progression.
Identifiants
pubmed: 36336987
doi: 10.1111/epi.17457
pmc: PMC9852002
mid: NIHMS1848126
doi:
Substances chimiques
TOR Serine-Threonine Kinases
EC 2.7.11.1
ANGPTL7 protein, human
0
Angiopoietin-like Proteins
0
Angiopoietin-Like Protein 7
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
218-230Subventions
Organisme : NINDS NIH HHS
ID : R01 NS123928
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG060882
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066512
Pays : United States
Informations de copyright
© 2022 International League Against Epilepsy.
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