ArticleAnnals of neurology2019
Functional deficiency in endogenous interleukin-1 receptor antagonist in patients with febrile infection-related epilepsy syndrome.
Article in Annals of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 111 citations in OpenAlex.
- Infection-triggered encephalopathy syndromes: a meta-analysis of clinical characteristics and outcomes in 1946 cases.EClinicalMedicine · 2026Article
- Standard complete blood count to predict long-term outcomes in febrile infection-related epilepsy syndrome (FIRES): A multicenter study.Epilepsia · 2025Article
- IL-1β and HMGB1 in Epileptogenesis: Recent Advances and Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Observational Study of Tocilizumab in Children With Febrile Infection-Related Epilepsy Syndrome.Annals of clinical and translational neurology · 2025Observational
- Minocycline in chronic management of febrile infection-related epilepsy syndrome (FIRES): a case series and literature review of treatment strategies.Acta epileptologica · 2025Review
- Adult-Onset Febrile Infection-Related Epilepsy Syndrome Treated with Short-Term Anakinra.Journal of epilepsy research · 2025Article
- A Case Series and Review of Febrile-Infection Related Epilepsy Syndrome (FIRES).Children (Basel, Switzerland) · 2025Review
- Combined Systemic Immunotherapy and Intrathecal Dexamethasone in Febrile Infection Related Epilepsy Syndrome.Annals of clinical and translational neurology · 2025Article
- Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.Neuron · 2025Review
- Early initiation of intravenous cyclophosphamide and one-year outcome in super-refractory cryptogenic-new onset refractory status epilepticus.Epilepsia open · 2025Article
- Cytokines in new-onset refractory status epilepticus: ready for clinical use?Acta epileptologica · 2024Article
- Article
- mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.Nature reviews. Neuroscience · 2024Review
- Case report: Febrile infection-related epilepsy syndrome in a 14-year-old girl with multiple organ failure and lethal outcome.Frontiers in neuroscience · 2024Article
- Bridging the Gap: Tailoring an Approach to Treatment in Febrile Infection-Related Epilepsy Syndrome.Neurology · 2023Article
- Cannabidiol in the acute phase of febrile infection-related epilepsy syndrome (FIRES).Epilepsia open · 2023Article
- Drug-resistant seizures associated with hyperinflammatory monocytes in FIRES.Annals of clinical and translational neurology · 2023Article
- Systemic inflammatory markers and EEG features of children with FIRES receiving anakinra.Annals of clinical and translational neurology · 2023Article
- Inflammation as Treatment Target for Status Epilepticus.Current neuropharmacology · 2023Article
- Seizure burden and neuropsychological outcomes of new-onset refractory status epilepticus: Systematic review.Frontiers in neurology · 2023Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveWe recently reported successful treatment of a child with febrile infection-related epilepsy syndrome (FIRES), a subtype of new onset refractory status epilepticus, with the recombinant interleukin-1 (IL1) receptor antagonist (IL1RA) anakinra. On this basis, we tested whether endogenous IL1RA production or function is deficient in FIRES patients.
methodsLevels of IL1β and IL1RA were measured in serum and cerebrospinal fluid (CSF). The inhibitory activity of endogenous IL1RA was assessed using a cell-based reporter assay. IL1RN gene variants were identified by sequencing. Expression levels for the secreted and intracellular isoforms of IL1RA were measured in patient and control cells by real-time polymerase chain reaction.
resultsLevels of endogenous IL1RA and IL1β were elevated in the serum and CSF of patients with FIRES (n = 7) relative to healthy controls (n = 10). Serum from FIRES patients drove IL1R signaling activity and potentiated IL1R signaling in response to exogenous IL1β in a cell-based reporter assay. Functional assessment of endogenous IL1RA activity in 3 FIRES patients revealed attenuated inhibition of IL1R signaling. Sequencing of IL1RN in our index patient revealed multiple variants. This was accompanied by reduced expression of intracellular but not secreted isoforms of IL1RA in the patient's peripheral blood mononuclear cells.
interpretationOur findings suggest that FIRES is associated with reduced expression of intracellular IL1RA isoforms and a functional deficiency in IL1RA inhibitory activity. These observations may provide insight into disease pathogenesis for FIRES and other inflammatory seizure disorders and may provide a valuable biomarker for therapeutic decision-making. Ann Neurol 2019;85:526-537.
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