Molecular and cellular evaluation in antibody-mediated autoimmune encephalitis

• Grant number: 20/14640-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 14, 2022
• End date: March 31, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Iscia Teresinha Lopes Cendes
• Grantee: Tânia Kawasaki de Araújo
• Supervisor: Sarosh Irani
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Oxford, England
• Associated to the scholarship: 17/01900-6 - Identification of the distribution of HLA alleles in the Brazilian population and in neurological phenotypes possibly associated with autoimmunity, BP.PD

Abstract

Autoantibody-mediated forms of encephalitis (AE) include neurological disorders characterized by subacute memory loss, movement disorders, and frequent, focal epileptic seizures. Objective: In this study, we aim to correlate phenotypes, immunological and genetic markers in our Brazilian patients with presumed AE. Methods: The cerebrospinal fluid (CSF), serum, and DNA samples of 50 patients with AE, nine patients with autoimmune epilepsy, five patients with Rasmussen encephalitis, four patients with Hashimoto encephalitis, and 298 healthy controls have been stored in our biorepository for analyses. These individuals were genotyped for HLA using next-generation sequencing (NGS) technology. Given that there are still controversies regarding the role of specific HLA alleles in these disorders, HLA-associations in a sizeable cohort of clinically well-characterized patients with AE and other neurological autoimmune diseases are critical to advance gain additional insights into the role of HLA as a predisposing factor to these disorders. This is especially relevant for admixed and underrepresented populations in these types of studies, such as for the Brazilian population. However, it is also essential that a thorough antibody characterization is performed in these samples in addition to a detailed clinical characterization. Thus, state-of-the-art immunocellular experiments will be performed to determine the autoantibodies involved in our samples. We expect that the results of this work will not only be relevant for the specific population studied, by will also improve our understanding of the relationship between genetic diversity, HLA alleles and neurological autoimmune disorders. (AU)