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João Chaves
Neurologist
Immunogenetic factors and neuroinflammation in two different types of epilepsy: Genetic generalized epilepsy and mesial temporal lobe epilepsy
What is the aim of your doctoral thesis?
Genetic generalized epilepsies (GGEs) are a group of epilepsy syndromes in which generalized seizures are the core symptom. The aim of this thesis was to investigate the role of immunogenetic factors, inflammatory molecules, and epigenetic factors in the development of GGEs and to identify possible biomarkers. We also compared our results with data from mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS).
What are the main findings of the study?
We demonstrated a protective role for HLA-DRB1*09, HLA-DRB1*13, and ApoE e3/e2 genotypes in GGEs. We observed that the rs16944 polymorphism of IL-1ß is not correlated with the development of GGEs. We demonstrated that the panel combining miR-146a, miR-155, and miR-132 has potential diagnostic value as a GGE biomarker. In MTLE-HS, we showed that circulating miR-22 levels were increasingly lower as the number of drugs used increased, suggesting that miR-22 may be a potential biomarker of pharmacoresistance in MTLE-HS. In the study of GGE comorbidities, we suggested that GGEs and autoimmune diseases (AIDs) have a bidirectional temporal relationship, while the relationship between MTLE-HS and AIDs is unidirectional.
What are the main conclusions of the study?
The main study conclusion is that immunogenetic factors and inflammatory molecules play different roles in the development of GGEs and MTLE-HS. Patients with GGEs seem to be better able to modulate and control the inflammatory response provided by the contribution of immunogenetic factors, which seem to have a protective role in these epilepsies. Moreover, these patients have an absence of predisposing inflammatory molecules. Conversely, patients with MTLE-HS have greater difficulty in controlling the inflammatory response because they have predisposing factors for its maintenance.
Full version available at: https://hdl.handle.net/10216/155244
João Chaves, an attending physician of Neurology at ULS Santo António, is particularly dedicated to epilepsy. He is a member of the Refractory Epilepsy Reference Center. He is responsible for the epilepsy in pregnancy consultation. He integrates the Multidisciplinary Biomedicine Research Unit at ICBAS-UP, where he collaborates in various epilepsy research projects. He completed his Ph.D. in Medical Sciences at ICBAS-UP in October 2023 under the supervision of Professor António Martins da Silva.
