Haematological and immunological mechanisms involved in the therapeutic response of patients with sickle cell anemia submitted to allogeneic hematopoietic stem cell transplantation

• Grant number: 14/00088-8
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2014
• Effective date (End): March 10, 2018
• Field of knowledge: Biological Sciences - Immunology
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Kelen Cristina Ribeiro Malmegrim de Farias
• Grantee: Júlia Teixeira Cottas de Azevedo
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID

Abstract

Sickle cell anemia (SCA) is a monogenic disease characterized by chronic hemolytic anemia and vaso-occlusive phenomena that lead to acute painful crises and to tissue and organ, chronic and progressive damage. It is the most common monogenic hereditary disease of Brazil, occurring predominantly among African descendants, it is heterogeneously distributed being more frequent in the North and Northeast. The available treatments for SCA are Hydroxyurea, blood transfusion and allogeneic hematopoietic stem cell transplantation (HSCT), which is the only curative option. This project aims to evaluate the haematological and immunological mechanisms in patients with SCA subjected to allogeneic HSCT. Patients with sickle cell anemia (HbS homozygotes) submitted to treatment with allogeneic HSCT in the Bone Marrow Transplantation Unit of the Clinical Hospital (FMRP-USP) will be studied. Peripheral blood samples of SCA patients will be collected before and at different times after transplantation, and then evaluated: I) immune-hematological reconstitution of various cell subpopulations in peripheral blood; II) expression of phosphatidylserine, CD47, and BCAM / LU erythrocytes, and further, CD36 and VLA-4 in reticulocyte; III) production of pro- and anti-inflammatory (IL-1² , IL-2 , IL-6 , IL-8 , IFN-³, TNF-± , IL -17A / F, IL-18 , G -CSF and IL-10) and sHLA-G; IV) biomarkers of SCA (lactate dehydrogenase [LDH], secretory phospholipase A2 [sPLA2], products of nitric oxide metabolism [nitrite and nitrate] and endothelin-1); V) the presence of polymorphisms in the 3'-NT region of HLA-G gene; VI) cell chimerism by analyzing STR and amelogenin locus; VII) the differential gene expression of microRNAs in erythrocytes CD45-CD71+. The results of this study might help to confirm the therapeutic benefits of allogeneic HSCT in the treatment of SCA and to elucidate the hematological and immunological mechanisms involved, which are extremely necessary for more extensive application of this cell therapy in patients with SCA. (AU)