Increased frequency of proinflammatory CD4 T cells and pathological levels of serum neurofilament light chain in adult drug-resistant epilepsy.
Adult
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes
/ immunology
Case-Control Studies
Cytokines
/ immunology
Drug Resistant Epilepsy
/ immunology
Epilepsy
/ drug therapy
Female
Flow Cytometry
Granulocyte-Macrophage Colony-Stimulating Factor
/ immunology
Humans
Immunoassay
Inflammation
Interferon-gamma
/ immunology
Interleukin-10
/ immunology
Interleukin-17
/ immunology
Interleukin-4
/ immunology
Interleukins
/ immunology
Male
Middle Aged
Neurofilament Proteins
/ immunology
Single Molecule Imaging
Th17 Cells
/ immunology
Th2 Cells
/ immunology
Tumor Necrosis Factor-alpha
/ immunology
Young Adult
Interleukin-22
CD4 T cells
drug-resistant epilepsy
inflammatory cytokines
serum neurofilament light chain (sNfL)
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
01
06
2020
revised:
02
10
2020
accepted:
07
10
2020
pubmed:
4
11
2020
medline:
20
4
2021
entrez:
3
11
2020
Statut:
ppublish
Résumé
Adult drug-resistant epilepsy (DRE) is associated with significant morbidity. Infiltration of immune cells is observed in DRE epileptic foci; however, the relation between DRE and the peripheral immune cell compartment remains only partially understood. We aimed to investigate differences in immune cell populations, cytokines, and neurodegenerative biomarkers in the peripheral blood of subjects with epilepsy versus healthy controls, and in DRE compared to well-controlled epilepsy (WCE). Peripheral blood mononuclear cells and serum from >120 age- and sex-matched adults suffering from focal onset epilepsy and controls were analyzed by multipanel flow cytometry, multiplex immunoassays, and ultrasensitive single molecule array. Using a data-driven analytical approach, we identified that CD4 T cells in the peripheral blood are present in a higher proportion in DRE patients. Moreover, we observed that the frequency of CD4 T cells expressing proinflammatory cytokines interleukin (IL)-17A, IL-22, tumor necrosis factor, interferon-γ, and granulocyte-macrophage colony-stimulating factor, but not anti-inflammatory cytokines IL-10 and IL-4, is elevated in the peripheral blood of DRE subjects compared to WCE. In parallel, we found that Th17-related circulating proinflammatory cytokines are elevated, but Th2-related cytokine IL-4 is reduced, in the serum of epilepsy and DRE subjects. As Th17 cells can exert neurotoxicity, we measured levels of serum neurofilament light chain (sNfL), a marker of neuronal injury. We found significantly elevated levels of sNfL in DRE compared to controls, especially among older individuals. Our data support that DRE is associated with an expansion of the CD4 Tcell subset in the peripheral blood and with a shift toward a proinflammatory Th17/Th1 CD4 Tcell immune profile. Our results further show that pathological levels of sNfL are more frequent in DRE, supporting a potential neurodegenerative component in adult DRE. With this work, we provide evidence for novel potential inflammatory and degenerative biomarkers in DRE.
Substances chimiques
CSF2 protein, human
0
Cytokines
0
IFNG protein, human
0
IL10 protein, human
0
IL17A protein, human
0
IL4 protein, human
0
Interleukin-17
0
Interleukins
0
Neurofilament Proteins
0
TNF protein, human
0
Tumor Necrosis Factor-alpha
0
neurofilament protein L
0
Interleukin-10
130068-27-8
Interleukin-4
207137-56-2
Interferon-gamma
82115-62-6
Granulocyte-Macrophage Colony-Stimulating Factor
83869-56-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
176-189Subventions
Organisme : Savoy Foundation
Informations de copyright
© 2020 International League Against Epilepsy.
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