21/10 – SEMINÁRIO DE QUALIFICAÇÃO (Doutorado) – Bruna Kulmann-Leal

21 de outubro de 2024 (segunda-feira)

10h30min

SEMINÁRIO DE QUALIFICAÇÃO (Doutorado)

BRUNA KULMANN-LEAL

Autism spectrum disorder: an assessment of immunogenetics and gene vs. environment relationships

Orientador: Dr. José Artur Bogo Chies

Banca Examinadora: Dra. Lavínia Schüler Faccini e Dra. Marcia Holsbach Beltrame

21 de outubro de 2024 (segunda-feira)

10h30min

Presencial: Anfiteatro do Departamento de Genética da UFRGS (Campus do Vale, prédio 43312)

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in communication and social interaction and the presence of stereotypical behaviors. The etiology of ASD is not fully established, but it is known that genetic and environmental factors influence the disorder. Environmental factors such as gestational problems and exposure to substances that interfere with neurodevelopment are strongly linked to the development of the disorder. Genes related to the immune system seem to be part of the pathophysiology of ASD. In this context, both qualitative and quantitative differences in immune responses have been demonstrated between children with ASD and typically developing controls. Chemokines and their receptors are important molecules, and, when we compare the chemokine profile of children with ASD and children with typical development, there are significant differences, such as in CCL3, CCL5, CCL8 and CCL11 levels. Also, evidence has indicated that CCR5 may have an influence on the pathogenesis of autism, but the relationship between CCR5 and ASD represents an open question. Thus, the present study aims to investigate the role of the CCR5 receptor and the chemokines CCL3, CCL5 and CCL8 in ASD, as well as to relate environmental factors that may play a relevant role in the pathogenesis of ASD. To this end, the genetic variant CCR5Δ32, which leads to non-expression of the CCR5 receptor, was evaluated in children diagnosed with ASD. In addition, an analysis of chemical substances that interact with CCL3, CCL5 and CCL8 genes and that also play a role in ASD was performed. This was an exploratory analysis, which aims to serve as a basis for review and discussion work. Furthermore, a sequencing analysis of the promoter region of the CCR5 gene will be performed, as well as a more robust analysis of the Δ32 variant with mothers and fathers of the diagnosed children. Review articles and commentaries are also part of this work. The article “Commentary on “Association between NKG2/KLR gene variants and epilepsy in Autism Spectrum Disorder”” was published in the Journal of Neurology & Neuromedicine, and a review proposal on microbiota and ASD was submitted for evaluation in the Journal of the American Academy of Child & Adolescent Psychiatry. Regarding the CCR5Δ32 variant, there was no statistically significant difference in the frequency found in the children evaluated compared to pre-existing data on the frequency found in Rio Grande do Sul. Analyses related to chemicals and their roles in ASD still need further investigation. Thus, the present work seeks to understand how chemokines and their receptors influence ASD, using variant studies, review works and exploratory analyses on chemicals.