Lymphocyte senescence profile analysis of adult patients with sickle cell anemia.

• Grant number: 24/08708-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Vanderson Geraldo Rocha
• Grantee: Guilherme Hirose
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cellular senescence is a physiological process associated with aging which is mainly characterized by the arrest of the cell cycle, metabolic and functional alterations and the acquisition of a pro-inflammatory secretory phenotype. However, stressors both internal and external to the cell can induce premature cellular senescence. Premature T-cell senescence has already been described in autoimmune and chronic inflammatory diseases, such as rheumatoid arthritis, HIV infection and in some cancer patients. In this scenario, sickle cell anemia (SCA) stands out as a chronic inflammatory disease. SCA is a genetic disease caused by a mutation in the gene encoding the ² subunit of hemoglobin. The altered hemoglobin (HbS) polymerizes inside the erythrocytes and induces conformational and metabolic changes that make the cells prone to intravascular hemolysis and adhesion to the endothelium and other blood cells. These events initiate processes of vaso-occlusion, followed by damage associated with ischemia and reperfusion that promote chronic inflammation, episodes of intense pain and dysfunction in different organs. Chronic inflammation and the constant stimulation of immune cells support the hypothesis that there is premature senescence of immune cells in patients with SCA. In this sense, a reduction in the telomere length of PBMCs and a higher percentage of CD4zCD28- T cells in these patients when compared to healthy individuals have already been described. Therefore, the aim of this project is to investigate the presence of senescent T lymphocytes in SCA patients undergoing different treatment regimens by means of phenotypic and functional analyses.