Advertisement

ResearchIn-Press PreviewImmunologyInflammationNeuroscience Open Access | 10.1172/jci.insight.200419

Systemic Immune Dysregulation and Neutrophil Activation Define Prognostic Inflammatory Signatures in Drug-Resistant Epilepsy

Coraly Simoës Da Gama,1 Aurelie Hanin,2 Gwen Goudard,3 Veronique Masson,3 Aurore Besnard,3 Karim Dorgham,4 Guy Gorochov,4 Guillaume Dorothee,1 Valerio Frazzini,2 Vincent Navarro,2 and Mélanie Morin-Brureau1

1Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), Hôpital Saint-Antoine, Paris, France

2Sorbonne Université, Paris Brain Institute, ICM, INSERM, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

3AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Paris, France

4Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP-HP, Département d’Immunologie, Hôpital de la Pitié-Salpêtrière, Paris, France

Find articles by Simoës Da Gama, C. in: PubMed | Google Scholar

1Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), Hôpital Saint-Antoine, Paris, France

2Sorbonne Université, Paris Brain Institute, ICM, INSERM, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

3AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Paris, France

4Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP-HP, Département d’Immunologie, Hôpital de la Pitié-Salpêtrière, Paris, France

Find articles by Hanin, A. in: PubMed | Google Scholar

1Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), Hôpital Saint-Antoine, Paris, France

2Sorbonne Université, Paris Brain Institute, ICM, INSERM, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

3AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Paris, France

4Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP-HP, Département d’Immunologie, Hôpital de la Pitié-Salpêtrière, Paris, France

Find articles by Goudard, G. in: PubMed | Google Scholar

1Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), Hôpital Saint-Antoine, Paris, France

2Sorbonne Université, Paris Brain Institute, ICM, INSERM, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

3AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Paris, France

4Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP-HP, Département d’Immunologie, Hôpital de la Pitié-Salpêtrière, Paris, France

Find articles by Masson, V. in: PubMed | Google Scholar

1Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), Hôpital Saint-Antoine, Paris, France

2Sorbonne Université, Paris Brain Institute, ICM, INSERM, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

3AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Paris, France

4Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP-HP, Département d’Immunologie, Hôpital de la Pitié-Salpêtrière, Paris, France

Find articles by Besnard, A. in: PubMed | Google Scholar

1Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), Hôpital Saint-Antoine, Paris, France

2Sorbonne Université, Paris Brain Institute, ICM, INSERM, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

3AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Paris, France

4Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP-HP, Département d’Immunologie, Hôpital de la Pitié-Salpêtrière, Paris, France

Find articles by Dorgham, K. in: PubMed | Google Scholar |

1Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), Hôpital Saint-Antoine, Paris, France

2Sorbonne Université, Paris Brain Institute, ICM, INSERM, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

3AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Paris, France

4Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP-HP, Département d’Immunologie, Hôpital de la Pitié-Salpêtrière, Paris, France

Find articles by Gorochov, G. in: PubMed | Google Scholar |

1Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), Hôpital Saint-Antoine, Paris, France

2Sorbonne Université, Paris Brain Institute, ICM, INSERM, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

3AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Paris, France

4Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP-HP, Département d’Immunologie, Hôpital de la Pitié-Salpêtrière, Paris, France

Find articles by Dorothee, G. in: PubMed | Google Scholar |

1Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), Hôpital Saint-Antoine, Paris, France

2Sorbonne Université, Paris Brain Institute, ICM, INSERM, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

3AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Paris, France

4Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP-HP, Département d’Immunologie, Hôpital de la Pitié-Salpêtrière, Paris, France

Find articles by Frazzini, V. in: PubMed | Google Scholar

1Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), Hôpital Saint-Antoine, Paris, France

2Sorbonne Université, Paris Brain Institute, ICM, INSERM, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

3AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Paris, France

4Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP-HP, Département d’Immunologie, Hôpital de la Pitié-Salpêtrière, Paris, France

Find articles by Navarro, V. in: PubMed | Google Scholar

1Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine (CRSA), Hôpital Saint-Antoine, Paris, France

2Sorbonne Université, Paris Brain Institute, ICM, INSERM, CNRS, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

3AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Paris, France

4Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP-HP, Département d’Immunologie, Hôpital de la Pitié-Salpêtrière, Paris, France

Find articles by Morin-Brureau, M. in: PubMed | Google Scholar

Published April 14, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.200419.
Copyright © 2026, Simoës Da Gama et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 14, 2026 - Version history
View PDF
Abstract

Systemic inflammation is now recognized as a key contributor to epilepsy pathophysiology, yet the role of innate immune cells, particularly neutrophils, remains poorly defined in epilepsy. While preclinical studies in rodent models have implicated neutrophils in seizure activity, their phenotype in human epilepsy has not been thoroughly investigated. In this study, we aimed to characterize systemic inflammatory profiles and neutrophil-associated immune signatures in the blood of patients with drug-resistant epilepsy, compared to healthy controls. We identified a systemic low-grade inflammatory profile in patients, characterized by elevated neutrophil-to-lymphocyte ratio, C-reactive protein, pro-inflammatory cytokines (IL-6, CXCL8/IL-8, TNF-α), and activated neutrophils (CXCR4+CD62Llow). Neutrophil phenotyping revealed two distinct immune profiles. Patients with longer disease duration exhibited a more immature systemic signature, characterized by immature neutrophils (CD15⁺CD10⁻), resting neutrophils (CXCR4⁺CD62L⁺), and elevated IL-6 levels. In contrast, patients with higher seizure frequency displayed a more inflammatory profile, marked by increased IL-12 and activated (CXCR4+CD62Llow) and hyperactivated (CXCR4highCD62Llow) neutrophil subsets. Moreover, elevated pre-surgical levels of inflammatory profile TNF-α, IL-6, and hyperactivated CXCR4high CD62Llow neutrophils were associated with seizure recurrence one year after surgery. This pioneering study highlights the heterogeneity of peripheral immune responses in drug-resistant epilepsy and identifies neutrophil-related signatures as promising prognostic biomarkers in this context.

Graphical Abstract
graphical abstract
Supplemental material

View

Version history
  • Version 1 (April 14, 2026): In-Press Preview
Advertisement
Advertisement