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RED BLOOD CELL ALLOIMMUNIZATION IN SICKLE CELL DISEASE: IDENTIFICATION OF RH VARIANTS AND IMMUNE MARKERS

Grant number: 17/26950-6
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2018
Effective date (End): October 31, 2021
Field of knowledge:Health Sciences - Collective Health - Public Health
Principal researcher:Simone Kashima Haddad
Grantee:Evandra Strazza Rodrigues Sandoval
Home Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil

Abstract

Red blood cell alloimmunization in sickle cell disease (SCD) affects more than 30% of individuals in transfusion therapy. It is the main complication related to blood transfusion in SCD and may be related to the antigenic disparity between donors and patients or with a deficiency in the control of the cellular immune response. The prophylaxis adopted to prevent alloimmunization is to supply red blood cell units compatible with the most immunogenic antigens; however, the occurrence of RHD/ RHCE gene variants often makes this strategy ineffective. As an alternative, some centers use genotyping, notwithstanding, most of the molecular assays used are unable to detect new mutations, predict null alleles, or even massively screening donors and patients quickly.Regarding the immunological profile, alloimmunized SCD patients present a quantitative and functional alteration in regulatory and effector T lymphocytes. Consequently, the production of antibodies and the synthesis of inflammatory cytokines may also exhibit altered activities. However, the timing and motive that makes immunological cellular activity pathogenic in these individuals are unknown. Thus, to understand the stages of red blood cell alloimmunization process in SCD patients, this proposal aims to evaluate the frequency, function of T cell population and profile of inflammatory cytokines. In addition, RHD/ RHCE gene variants will also be determined in red blood cell alloimmunized SCD patients by next generation sequencing.

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