Association between arbovirus infection and autoimmune encephalitis

• Grant number: 20/07140-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2020
• Effective date (End): August 31, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Livia Almeida Dutra
• Grantee: Bruna de Freitas Dias
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil

Abstract

Autoimmune encephalitis (AIE) is the main cause of non-infectious encephalitis and results from a peripheral immune response against central nervous system (CNS) antigens, with the production of autoantibodies directed against cell surface antigens. The clinical manifestations of AIE are varied and include cognitive complaints, behavioral changes such as psychosis, apathy and catatonia; movement disorders, epilepsy, diarrhea, polyneuropathy, sleep disorders and acute or subacute ventilation. Some tumors (breast, pulmonary and ovarian cancer a well as thymoma) and viral infections of the CNS are considered as triggers for AIE. Some neurotropic viruses, such as herpes family, can trigger the production of antineuronal antibodies. Arboviruses, represented in Brazil by Zika (ZIKV), Dengue (DENGV) and Chikungunya (CHIKV) viruses, are also neurotropic infections and present with neurological manifestations such as myelitis, encephalitis, cranial neuritis and acute polyradiculoneuritis such as Guillain Barré syndrome. The pathophysiological mechanism of such manifestations is unknown.Objective: To verify the association between AIE and arboviroses in the Brazilian population. The current project is an arm of the ongoing project called "Autoimmune encephalitis in Brazil: clinical description, development of innovative methodological platforms and evaluation of viral triggers". It is a multicentric study consisting of two arms: the first aims to study the cases of autoimmune encephalitis in Brazil, with its characteristics, clinical and allowing the formation of a network of researchers in autoimmune encephalitis. The second aims to verify the association between antibodies against viruses of the herpes family and arboviruses (CHIK, DENG and ZIK) in patients with autoimmune encephalitis. The scholarship request for the student refers to the study arm focused on the association between arboviruses and autoimmune encephalitis. Suspected patients who meet the criteria for probable autoimmune encephalitis assessed at the 18 centers of Brazilian Autoimmune Encephalitis Network (BrAIN network) will be included. Clinical, epidemiological and laboratory data will be compiled and compared using the Mann-Whitney, Student's T and chi-square tests. Antineuronal antibodies will be detected using immunohistochemistry techniques in the rat brain, followed by cell-based assay (CBA) and immunoblot in serum and CSF samples. PCR (Polymerase Chain Reaction), PCR-RT, (Real-time Polymerase Chain Reaction) and ELISA (Enzyme-Linked Immunosorbent Assay) will also be performed to detect antibodies against ZIKV, DENGV and CHIKV. Kaplan-Meyer curves and log tests will be calculated. P <0.05 will be considered significant.