Genetic-molecular investigation of SCID patients; Immunopathology, comorbidities, and genetic susceptibility to zika virus infection in humans

Abstract

Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic diseases with repercussions on the immune response. Severe combined immunodeficiency (SCID) is characterized by high T lymphocyte deficiency, which affects cellular and humoral immunity, and generates severe abnormalities in the development and functions of the immune system. Newborns with SCID present the disease in the first months of age and are highly susceptible to infections. Without treatment, these conditions are invariably fatal, making SCID a pediatric emergency.Transplantation with hematopoietic stem cells does not depend on the discovery of the molecular defect involved, but this research is important because it represents a prerogative for gene therapy, genetic counseling and prenatal diagnosis. Thus, this work aims to investigate genetic-molecular defects of patients with SCIDs identified through neonatal screening (previously supported by FAPESP 2012 / 51233-2) or referred by physicians from different regions of the country. With this, it is expected to expand the knowledge about this disease, adding to the still incipient information about the epidemiology of SCID in Brazil and to contributing to the development and improvement of diagnostic methods and treatments for the affected individuals in order to improve their quality of life, as well as genetic counseling for families.Considering the severity of the outbreak caused by ZIKV in Brazil and its complications, such as Guillain-Barré syndrome and microcephaly, it is necessary to study the immune response to this pathogen, especially those with a focus on resistance or susceptibility genes . Therefore, understanding the importance of the synthesis and signaling pathways of type I IFNs in this context, we propose to search for genetic mapping, resistance markers and susceptibility in patients infected by ZIKV. In addition, we intend in parallel to transpose the results obtained for verification in an experimental model, using the experimental models already established in our laboratory.