Multidimensional Approach Assessing the Role of Interleukin 1 Beta in Mesial Temporal Lobe Epilepsy

Renato O Santos; Rodrigo Secolin; Patrícia G Barbalho; Mariana S Silva-Alves; Marina K M Alvim; Clarissa L Yasuda; Fábio Rogerio; Tonicarlo R Velasco; Americo C Sakamoto; Antonio L Teixeira; Fernando Cendes; Claudia V Maurer-Morelli; Iscia Lopes-Cendes

doi:10.3389/fneur.2021.690847

Multidimensional Approach Assessing the Role of Interleukin 1 Beta in Mesial Temporal Lobe Epilepsy

Front Neurol. 2021 Aug 5:12:690847. doi: 10.3389/fneur.2021.690847. eCollection 2021.

Authors

Renato O Santos^{1

2}, Rodrigo Secolin^{1

2}, Patrícia G Barbalho^{1

2}, Mariana S Silva-Alves^{1

2}, Marina K M Alvim^{2

3}, Clarissa L Yasuda^{2

3}, Fábio Rogerio^{2

4}, Tonicarlo R Velasco⁵, Americo C Sakamoto⁵, Antonio L Teixeira⁶, Fernando Cendes^{2

3}, Claudia V Maurer-Morelli^{1

2}, Iscia Lopes-Cendes^{1

2}

Affiliations

¹ Department of Translational Medicine, University of Campinas, Campinas, Brazil.
² Brazilian Institute of Neuroscience and Neurotechnology, Campinas, Brazil.
³ Department of Neurology, University of Campinas, Campinas, Brazil.
⁴ Department of Pathology, University of Campinas, Campinas, Brazil.
⁵ Department of Neuroscience and Behavioral Science, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
⁶ Department of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.

Abstract

We aimed to investigate the role of interleukin-1 beta (IL-1β) in the mechanisms underlying mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). We assessed a cohort of 194 patients with MTLE+HS and 199 healthy controls. Patients were divided into those with positive and negative antecedent febrile seizures (FS). We used a multidimensional approach, including (i) genetic association with single nucleotide polymorphisms (SNPs) in the IL1B gene; (ii) quantification of the IL1B transcript in the hippocampal tissue of patients with refractory seizures; and (iii) quantification of the IL-1β protein in the plasma. We found a genetic association signal for two SNPs, rs2708928 and rs3730364^*C in the IL1B gene, regardless of the presence of FS (adjusted p = 9.62e-11 and 5.14e-07, respectively). We found no difference between IL1B transcript levels when comparing sclerotic hippocampal tissue from patients with MTLE+HS, without FS, and hippocampi from autopsy controls (p > 0.05). Nevertheless, we found increased IL-1β in the plasma of patients with MTLE+HS with FS compared with controls (p = 0.0195). Our results support the hypothesis of a genetic association between MTLE+HS and the IL1B gene.

Keywords: association study; gene expression; hippocampal atrophy; mesial temporal sclerosis; neuroinflammation.