Evaluation of thymic function in patients with sickle cell anemia

Abstract

Sickle cell anemia (SCA) is the most common monogenic disease in the world , with important clinical, epidemiological and social impact. In Brazil, is the most common hereditary disease, occurring predominantly among Afrodescendants. The disease is characterized by chronic hemolytic anemia, chronic inflammatory and procoagulant state, and vaso-occlusive phenomena that lead to acute painful crises and damage tissue, chronic and progressive to multiple organs and a broad spectrum of clinical complications. Among the available treatments for AF there are: hydroxyurea, blood transfusions and of allogeneic hematopoietic stem cell transplantation (HSCT). Hydroxyurea, although it benefits an important number of patients, has its indications and limitations. Already blood transfusion is used only in special circumstances, and, both therapies not revert completely the inflammatory state. Thus, allogeneic HSCT is the only curative option for these patients. It is known that the thymus is an organ of paramount importance in the prevention and control of infections. While virtually all organs are affected in SCA , currently, there are no data in the literature about how the disease affects the thymus and its function. Thus, it is extremely important to evaluate thymic function in these patients. After allogeneic HSCT, thymic reactivation is critical to the quality of immune reconstitution and correlates with patient survival , occurrence of serious infections and clinical outcome . Therefore, this present project has the general objective to evaluate thymic function in patients with sickle cell anemia before and after treatment with hydroxyurea, before and after treatment with allogeneic HSCT, untreated patients and in healthy subjects controls. For this, will be assessed in these groups: I) absolute expression of T cell excision circles ( TRECs ) in peripheral blood T cells; II) analysis of the diversity of the repertoire of T cells; III) serum levels of agents "thymus -stimulators" IL-7, IL-22, KGF (keratinocyte growth fator), leptina, hGH (human growth hormone), TSLP (thymic stromal lymphopoietin) e "timo-supressores" IL-6, LIF (leukemia inhibitory fator) e OSM (oncostatin M), iv) correlation of laboratory findings with the clinical assessment of patients. This study will help to unravel if the thymic function is defective in patients with SCA, and, if the current treatments for this disease, improve the thymic function in these patients, opening possibilities for others therapeutic interventions. Furthermore, this study will contribute to the elucidation of the immunological mechanisms of action involved in allogeneic HSCT in the treatment of SCA, the only curative treatment for SCA, which is necessary for a wider and effective application of this therapy in patients with SCA. (AU)