Evaluation of immune reconstitution and thymic function in sickle cell disease patients submitted to allogeneic hematopoietic stem cell transplantation

• Grant number: 16/22330-0
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2017
• End date: March 31, 2019
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Kelen Cristina Ribeiro Malmegrim de Farias
• Grantee: Kelen Cristina Ribeiro Malmegrim de Farias
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Ana Cristina Silva Pinto ; Belinda Pinto Simoes ; Dimas Tadeu Covas

Abstract

Sickle cell disorders (SCD) refers to a set of hemoglobinopathies (hereditary disorders of hemoglobin) caused by a point mutation at position 6 of the gene encoding the chain ²-globin, leading to physical-chemical changes in the hemoglobin molecule, yielding hemoglobin (Hb) abnormally S (HbS). The form of the disease where the two encoders of ²-globin alleles are mutated (i.e. are homozygous HBSS) is called sickle cell anemia (SCA) and occurs in approximately 83% of cases. Despite its high incidence, SCA is a neglected disease with great social impact, with few resources available for diagnosis, treatment and research in Brazil and the world. In recent years, cell therapy with allogeneic hematopoietic stem cell (or allogeneic hematopoietic stem cell transplantation, HSCT) has emerged as an alternative therapy. Despite limited number of patients were transplanted, there is an evident curative potential of this new therapeutic approach. However, there are no studies on immune reconstitution mechanisms after HSCT in patients with SCA. Considering our hypothesis that patients with SCA have a significant thymic and immune dysfunction, it is extremely important and urgent to assess the impact of these dysfunctions in the immune reconstitution and cell chimerism processes in SCA patients after HSCT. The results of this study will certainly help to confirm whether the clinical-laboratorial benefits of HSCT in SCA patients are superior than other therapeutic modalities, which is required for a wider application of this cell therapy in patients with SCA. (AU)