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Increased frequency of proinflammatory CD4 T cells and pathological levels of serum neurofilament light chain in adult drug‐resistant epilepsy
Author(s) -
Ouédraogo Oumarou,
Rébillard RoseMarie,
Jamann Hélène,
Mamane Victoria Hannah,
Clénet MarieLaure,
Daigneault Audrey,
Lahav Boaz,
Uphaus Timo,
Steffen Falk,
Bittner Stefan,
Zipp Frauke,
Bérubé Arline,
LapalmeRemis Samuel,
Cossette Patrick,
Nguyen Dang Khoa,
Arbour Nathalie,
Keezer Mark R.,
Larochelle Catherine
Publication year - 2021
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.16742
Subject(s) - proinflammatory cytokine , epilepsy , medicine , immune system , immunology , cytokine , peripheral blood mononuclear cell , tumor necrosis factor alpha , inflammation , biology , psychiatry , biochemistry , in vitro
Objective 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). Methods 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. Results 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. Significance 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.