RHD and RHCE genotyping by next-generation sequencing is an effective strategy to identify molecular variants within sickle cell disease patients

Dezan, Marcia Regina; Ribeiro, Ingrid Helena; Oliveira, Vítor Hugo de; Vieira, Juliana Borges; Gomes, Francisco C. A.; Franco, Lucas Augusto Moysés; Varuzza, Leonardo; Ribeiro, Roberto; Chinoca, Karen Z.; Levi, José Eduardo; Krieger, José Eduardo; Pereira, Alexandre C.; Gualandro, Sandra Fátima Menosi; Rocha, Vanderson; Mendrone‐Júnior, Alfredo; Sabino, Éster Cerdeira; Dinardo, Carla Luana

doi:10.1016/j.bcmd.2017.03.014

Cited by 29 publications

(31 citation statements)

References 22 publications

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“…Brazil represents one of the most diverse populations in the world, result of centuries of inter‐ethnical crossing of individuals from several continents . This ancestry diversity is a major factor underlying the peculiar distribution of RBC antigen phenotype among Brazilians, especially referring to the RH system, in which both African and European genomes are represented . This miscegenation can be clearly demonstrated by the allele distribution found in the present study, which comprised individuals with weak‐D phenotype.…”

Section: Discussionsupporting

confidence: 48%

High frequency of variant RHD genotypes among donors and patients of mixed origin with serologic weak‐D phenotype

Dezan

Oliveira

Gomes

et al. 2018

Clinical Laboratory Analysis

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Section: Discussionsupporting

confidence: 48%

High frequency of variant RHD genotypes among donors and patients of mixed origin with serologic weak‐D phenotype

Dezan

Oliveira

Gomes

et al. 2018

Clinical Laboratory Analysis

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“…To standardize the RFLP‐PCR assay, 15% of the included samples were tested in parallel using this method and conventional Sanger sequencing, which was considered the gold‐standard. Sanger sequencing was performed as described elsewhere (Dezan et al., ), using the same set of primers.…”

Section: Methodsmentioning

confidence: 99%

‐318C/T polymorphism of the CTLA‐4 gene is an independent risk factor for RBC alloimmunization among sickle cell disease patients

Oliveira

Dezan

Gomes

et al. 2017

Int J Immunogenetics

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Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) molecule is expressed on T-lymphocyte membrane and negatively influences the antigen-presenting process. Reduced expression of CTLA-4 due to gene polymorphisms is associated with increased risk of autoimmune disorders, whose physiopathology is similar to that of post-transfusion red blood cell (RBC) alloimmunization. Our goal was to evaluate if polymorphisms of CTLA-4 gene that affect protein expression are associated with RBC alloimmunization. This was a case-control study in which 134 sickle cell disease (SCD) patients and 253 non-SCD patients were included. All patients were genotyped for the polymorphisms 49A/G and -318C/T of CTLA-4 gene. The genotype frequency of -318C/T differed significantly between alloimmunized and nonalloimmunized SCD patients, irrespective of clinical confounders (p = .016). SCD patients heterozygous for -318T allele presented higher risk of alloantibody development (OR: 5.4, CI: 1.15-25.6). In conclusion, the polymorphism -318C/T of CTLA-4 gene is associated with RBC alloimmunization among SCD patients. This highlights the role played by CTLA-4 on post-transfusion alloantibody development.

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“…Recently, we have evaluated 35 SCD patients with unexplained Rh antibody, meaning they exhibited a certain Rh antibody in the sera but phenotyped as antigen-positive, using a NGS-based strategy in the Ion Torrent system (Thermo Fisher Scientific, Waltham, MA, USA) [27]. RHD*weak D 4.2.2 was the most common RHD variant allele (50%), followed by RHD*weak partial D 4.0 (20%), RHD*DVII (10%), and RHD*DAU0.01 (10%); and the most prevalent RHCE -altered alleles were RHCE*ce48C (40%), RHCE*ceAR (20%), and RHCE*ce 48C,733G (8%).…”

Section: Antigen-matching In Sickle Cell Disease Patients: Challengesmentioning

confidence: 99%

Optimized Antigen-Matched in Sickle Cell Disease Patients: Chances and Challenges in Molecular Times - the Brazilian Way

Castilho

Dinardo

2018

Transfus Med Hemother

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The development of red blood cell (RBC) alloantibodies and autoantibodies complicates transfusion therapy in sickle cell disease (SCD) patients. In an effort to reduce the risk of alloimmunization, some strategies have been used to provide antigen-matched RBC transfusions to patients with SCD in Brazil, including molecular matching in 3 levels: RH and K matching; extended matching (RH, KEL, FY, JK, MNS, DI), and extended matching including RHD and RHCE variant alleles. Molecular matching has shown clinical benefits to the patients with SCD, contributing significantly to reduce the rates of alloimmunization. Improvements in the clinical outcomes of the patients have also been observed as shown by an increase in their hemoglobin levels and reduction in their percentage of hemoglobin S as well as better in vivo RBC survival and diminished frequency of transfusions. However, prevention of RBC alloimmunization still remains a challenge in Brazil due to the difficulty to fulfill all transfusion requests of the patients with antigen-matching units, inaccuracy of RBC phenotyping, RBC transfusions outside the institution where the patient is treated, advanced age of some patients, the RBC antigen discrepancy between donors and recipients, and the presence of RH variants.

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RHD and RHCE genotyping by next-generation sequencing is an effective strategy to identify molecular variants within sickle cell disease patients

Cited by 29 publications

References 22 publications

High frequency of variant RHD genotypes among donors and patients of mixed origin with serologic weak‐D phenotype

High frequency of variant RHD genotypes among donors and patients of mixed origin with serologic weak‐D phenotype

‐318C/T polymorphism of the CTLA‐4 gene is an independent risk factor for RBC alloimmunization among sickle cell disease patients

Optimized Antigen-Matched in Sickle Cell Disease Patients: Chances and Challenges in Molecular Times - the Brazilian Way

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