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

Oliveira, Vítor Hugo de; Dezan, Marcia Regina; Gomes, Francisco C. A.; Gualandro, Sandra Fátima Menosi; Pereira, Alexandre C.; Marsiglia, Júlia Daher Carneiro; Levi, José Eduardo; Rocha, Vanderson; Mendrone‐Júnior, Alfredo; Sabino, Éster Cerdeira; Dinardo, Carla Luana

doi:10.1111/iji.12334

Cited by 20 publications

(18 citation statements)

References 26 publications

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“…Several factors are known to influence the recipient‘s immune system to react to alloantigens, e.g., the dose, the immunogenicity of the antigen as well as genetic or acquired patient-related factors [16,17,18,19,20,21]. However, possible differences in the immune makeup of transfused patients who produce alloantibodies (responders) and those who do not (non-responders) are not known.…”

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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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: 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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“…Genetic association studies aiming to identify predictive markers for alloimmunization are predominantly performed on small cohorts (N < 150) in which only a few variations are genotyped (Alarif et al, 1986;Chiaroni et al, 2006;Tatari-Calderone et al, 2009;Tatari-Calderone et al, 2013;Oliveira et al, 2017). To date, only one case-control genome-wide association study (GWAS) has been performed of alloimmune responder status in a cohort of 94 SCD patients (Hanchard et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Statistical power of genetic association studies depends on the number of tested markers, the SNP frequency and effect size of the SNP. Our cohort is currently the largest SCD cohort in literature with a relatively large study population of 275 SCD patients with a reasonably large number of cases (n = 145) (Hoppe et al, 2009;Tatari-Calderone et al, 2009;Hanchard Protective effect Tatari-Calderone et al, 2016;Fasano et al, 2017;Meinderts et al, 2017;Oliveira et al, 2017;Sippert et al, 2017). While this cohort was suitable to identify strong to moderate associations of SNPs with a reasonable frequency, weak associations may have been missed due to sample size.…”

Section: Snps For Quality Control 849 Candidate Snpsmentioning

confidence: 99%

“…We have previously reported that a mutation in FCGR2C is associated with a decreased risk of alloimmunization (Meinderts et al , ). Other groups have found that certain human leucocyte antigen (HLA) types or variations in TRIM21 , CD81 , TNF , IL1B and CTLA4 are potential risk factors for alloimmunization in SCD (Alarif et al , ; Reviron et al , ; Chiaroni et al , ; Noizat‐Pirenne et al , ; Hoppe et al , ; Picard et al , ; Tatari‐Calderone et al , ; Tatari‐Calderone et al , ; Sippert et al , ; Oliveira et al , ).…”

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Identification of genetic biomarkers for alloimmunization in sickle cell disease

et al. 2019

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Summary Most sickle cell disease (SCD) patients rely on blood transfusion as their main treatment strategy. However, frequent blood transfusion poses the risk of alloimmunization. On average, 30% of SCD patients will alloimmunize while other patient groups form antibodies less frequently. Identification of genetic markers may help to predict which patients are at risk to form alloantibodies. The aim of this study was to evaluate whether genetic variations in the Toll‐like receptor pathway or in genes previously associated with antibody‐mediated conditions are associated with red blood cell (RBC) alloimmunization in a cohort of SCD patients. In this case‐control study, cases had a documented history of alloimmunization while controls had received ≥20 RBC units without alloantibody formation. We used a customized single nucleotide polymorphism (SNP) panel to genotype 690 SNPs in 275 (130 controls, 145 cases) patients. Frequencies were compared using multiple logistic regression analysis. In our primary analysis, no SNPs were found to be significantly associated with alloimmunization after correction for multiple testing. However, in a secondary analysis with a less stringent threshold for significance we found 19 moderately associated SNPs. Among others, SNPs in TLR1/TANK and MALT1 were associated with a higher alloimmunization risk, while SNPs in STAM/IFNAR1 and STAT4 conferred a lower alloimmunization risk.

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

Cited by 20 publications

References 26 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

Identification of genetic biomarkers for alloimmunization in sickle cell disease

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

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

Cited by 20 publications

References 26 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

Identification of genetic biomarkers for alloimmunization in sickle cell disease

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