Evaluation of the Thymic Function in patients with sickle cell anemia following hematopoietic stem cell transplantation and conventionally treated

• Grant number: 16/11544-0
• Support type: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): October 16, 2016
• Effective date (End): April 15, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal researcher: Kelen Cristina Ribeiro Malmegrim de Farias
• Grantee: Luciana Ribeiro Jarduli
• Supervisor abroad: Antoine Toubert
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Hôpital Saint-Louis, France
• Associated to the scholarship: 14/03866-1 - Evaluation of thymic function in patients with sickle cell anemia, BP.DR

Abstract

Sickle cell anemia (SCA) is a hereditary chronic condition disorder of hemoglobin (Hb) caused by a single missense mutation in the human ²-globin gene, resulting in the formation of an abnormal hemoglobin (HbS). The polymerization of the HbS under hypoxic conditions is a key event in the complex pathophysiology of SCA. In Brazil, it is related one new case of SCA in every 1000 births, showing as a serious public health problem. Currently, the available treatments for SCA are Hydroxyurea (HU), Chronic Red Blood Cells (RBC) Transfusion and the Allogeneic Hematopoietic Stem cell Transplantation (allo-HSCT), that is the more established form of cell therapy and it is the only known curative treatment for SCA. The thymus plays a crucial role in the quality of immune reconstitution and clinical outcome after allo-HSCT, the reconstitution of a diversified repertoire of peripheral T cells is a long and continuous process that depends on a functional thymus, able to recover the completely ontogenesis of T and B cells. Patients with SCA are known to have altered immune systems; the disease itself is a pro-inflammatory condition. In this project, we hypothesized it is possible that the T cell defect in SCA patients may occur at multiple levels, including egress from the thymus and these patients may have functional abnormalities in the T and B cell ontogenesis. The aim of this project is to unravel if the thymic function is defective in patients with SCA and if the current treatments can improve the thymic function. In addition, it will focus on B and T cell reconstitution, especially the role played by the thymus in allo-HSCT, to understand the immunological mechanisms for the only curative treatment for SCA. (AU)