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Analysis of genetic polymorphisms associated with red blood cell alloimmunization and development of reference panels for RH genotyping to improve transfusion outcomes in patients with sickle cell disease

Abstract

Patients with sickle cell anemia are among one of transfused populations more often alloimmunized to red blood cell (RBC) antigens. With a better understanding of the genetic factors that predispose RBC alloimmunization, it will be possible to devise strategies of blood transfusions that will reduce the risk of alloimmunization and adverse reactions to transfusion. The molecular analysis of blood groups and Rh variants have proven to be useful in the identification of blood donors that are more likely to match patients with Sickle Cell Disease (SCD). However, the lack of reference panels for genotyping of Rh variants poses a significant challenge to the development and use of molecular testing devices. In this project, it is our intention to examine association between polymorphisms of genes RHAG, GZMB and PRKCQ with RBC alloimmunization and to develop panels of reference that are designed to include genotypes associated with RhD and RhCE variants more often found in this population of patients. Donors will be selected from a large donor pool based on historical and current serological and molecular typing information. To make DNA reference panels we will establish lymphoblastoid cell lines by Epstein-Barr virus (EBV) transformation so that we can have an unlimited supply of genomic DNA from the same source. We will carry out a national and international study with collaborating laboratories to obtain consensus typing results for each genotype, and to test the suitability of these panels as reference material. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MACEDO, MAYRA D.; MIRANDA, MARIA R.; SANTOS, TAMIRES D.; LEAL, IANCA; CASTILHO, LILIAN. Rh antibodies as a result of altered Rh epitopes on transfused red cells: a case series of seven Brazilian patients. BLOOD TRANSFUSION, v. 19, n. 5, p. 413-419, SEP-OCT 2021. Web of Science Citations: 0.
MENEGATI, SHEILA F. P.; SANTOS, TAMIRES D.; MACEDO, MAYRA D.; CASTILHO, LILIAN. Discrepancies between red cell phenotyping and genotyping in daily immunohematology laboratory practice. TRANSFUSION AND APHERESIS SCIENCE, v. 59, n. 1 FEB 2020. Web of Science Citations: 0.
SANTOS, T. D.; MACEDO, M. D.; MENEGATI, S. F. P.; GILLI, S.; CASTILHO, L. Challenges in providing compatible blood with Rh genotype-matching in Brazilian patients with sickle cell disease. Transfusion Medicine, OCT 2019. Web of Science Citations: 0.
GASPARDI, ANE C.; SIPPERT, EMILIA A.; DE MACEDO, MAYRA DORIGAN; PELLEGRINO, JR., JORDAO; COSTA, FERNANDO F.; CASTILHO, LILIAN. Clinically relevant RHD-CE genotypes in patients with sickle cell disease and in African Brazilian donors. BLOOD TRANSFUSION, v. 14, n. 5, p. 449-454, 2016. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.