Red blood cell alloimmunization in patients with sickle cell disease: correlation with HLA and cytokine gene polymorphisms

Sippert, Emília; Visentainer, Jeane Eliete Laguila; Alves, Hugo Vicentin; Rodrigues, Camila; Gilli, Simone Cristina Olenscki; Addas‐Carvalho, Marcelo; Saad, Sara T.O.; Costa, Fernando Ferreira; Castilho, Lilian

doi:10.1111/trf.13920

Cited by 51 publications

(71 citation statements)

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“…The incidence of alloimmunization in patients with SCD in Brazil ranges from 10 to 60% depending on the region and on the protocol of antigen matching used [4,5,6,7,8]. Even though our population is very mixed, we have observed that patients and donors exhibit differences in their genotype frequencies what could explain the high rates of alloimmunization in some regions [4,7].…”

Section: Introductionmentioning

confidence: 82%

“…In previous studies, we found that TNFA -308A, IL1B -511T, RHAG 808G>A and HLA-DRB1*15 alleles may predict a good responder phenotype [8] and that RHAG 808G>A and HLA-DRB*15 alleles are closely linked to RH alloimmunization [8,22]. These findings contributed to the development of a transfusion strategy for non-alloimmunized SCD patients as typing for these polymorphisms could potentially help in the classification of responder and non-responder SCD patients, allowing blood with high level of compatibility to be transfused to responders in order to avoid production of RBC antibodies and the negative consequences of alloimmunization.…”

Section: Antigen-matched In Sickle Cell Disease Patients: Chancesmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 82%

Section: Antigen-matched In Sickle Cell Disease Patients: Chancesmentioning

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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“…Identifying molecular markers to predict RBC alloimmunization relies on the fact that <20% of the transfusion recipients have the ability to develop alloantibodies after antigen‐mismatched transfusions (Higgins & Sloan, )and that patients’ genetic background is an important factor driving this susceptibility (Dinardo et al., ; Sippert et al., ). Our study is the first to evaluate the role played by polymorphisms on CTLA‐4 co‐stimulatory molecule on the alloimmunization scenario, demonstrating the association between ‐318C/T polymorphism, which modifies the expression of CTLA‐4 molecule on the cell surface, and the risk of post‐transfusion antibody development.…”

Section: Discussionmentioning

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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“…Overall, 21% of patients who have produced an RBC alloantibody produce additional alloantibodies after subsequent transfusion episodes . The genetic factors involved in RBC alloimmunization include HLA and non‐HLA genes . It should be noted that three of the four previously immunized patients had anti‐S antibodies, a specificity known to be frequently associated with multiple alloimmunization .…”

Section: Discussionmentioning

confidence: 99%

Predisposing factors for anti‐D immune response in D⁻ patients with chronic liver disease transfused with D⁺ platelet concentrates

et al. 2019

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BACKGROUND Recent reports have indicated that the risk of anti‐D alloimmunization following D‐incompatible platelet (PLT) transfusion is low in hematology and oncology patients. We investigated the rate of anti‐D alloimmunization in RhD‐negative (D−) patients with chronic liver disease transfused with D+ platelet concentrates (PCs) and the factors involved, at a liver transplant (LT) center. STUDY DESIGN AND METHODS We reviewed the blood bank database from January 2003 to October 2016. D− patients who had received D+ PLT transfusions were eligible if they had undergone antibody screening at least 28 days after the first D+ PC transfusion, had no previous or concomitant exposure to D+ blood products, and had not received anti‐D immunoglobulins. RESULTS Six of the 56 eligible patients (10.7%) had anti‐D antibodies. All had received whole blood‐derived PCs. Four of 20 patients (20%) untransplanted or transfused before LT and only two of 36 patients (5.6%) transfused during or after LT produced anti‐D antibodies. These two patients were on maintenance immunosuppression based on low‐dose steroids and tacrolimus. The factors identified as significantly associated with anti‐D immune response were the presence of red blood cell immune alloantibodies before D+ PLT transfusion (p = 0.003), and D+ PLT transfusion outside the operative and postoperative (5 days) periods for LT (p = 0.023). CONCLUSION D− patients with chronic liver disease transfused with D+ PLTs before LT are at high risk of developing anti‐D antibodies. Preventive measures should be considered for these patients.

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Red blood cell alloimmunization in patients with sickle cell disease: correlation with HLA and cytokine gene polymorphisms

Cited by 51 publications

References 87 publications

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

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

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

Predisposing factors for anti‐D immune response in D⁻ patients with chronic liver disease transfused with D⁺ platelet concentrates

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Red blood cell alloimmunization in patients with sickle cell disease: correlation with HLA and cytokine gene polymorphisms

Cited by 51 publications

References 87 publications

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

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

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

Predisposing factors for anti‐D immune response in D− patients with chronic liver disease transfused with D+ platelet concentrates

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Predisposing factors for anti‐D immune response in D⁻ patients with chronic liver disease transfused with D⁺ platelet concentrates