Understanding population-wide haplotype frequencies of human leukocyte antigen (HLA) alleles in linkage disequilibrium is important for hematopoietic stem cell transplantation

Otegbeye, Folashade

doi:10.1016/j.bjhh.2017.02.003

Cited by 2 publications

(2 citation statements)

References 10 publications

(12 reference statements)

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“…Several studies indicate that CD28, CTLA4, TNFSF4, and PDCD1 play important roles in the immune system and transplantations ( 21 – 23 ). In addition, genetic variants such as single-nucleotide polymorphisms (SNPs) in HLA and non-HLA regions have been linked to the success or failure of HSCT among different ethnic populations ( 24 , 25 ). In this study, we explored the association between donor SNPs of co-stimulatory genes (CTLA4, CD28, TNFSF4, and PDCD1) and the mortality, CMV infection, GVHD, and relapse of their corresponding recipients in the Taiwanese population.…”

Section: Introductionmentioning

confidence: 99%

The Association Between Single-Nucleotide Polymorphisms of Co-Stimulatory Genes Within Non-HLA Region and the Prognosis of Leukemia Patients With Hematopoietic Stem Cell Transplantation

et al. 2021

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To avoid graft rejection, the hematopoietic stem cells with matched classical human leukocyte antigen (HLA) alleles are the primary choice for clinical allogeneic transplantation. However, even if the fully HLA-matched hematopoietic stem cells are used for transplantation, some patients still have poor prognosis after hematopoietic stem cell transplantation (HSCT), suggesting that the HLA system was not the only determinant of the outcomes of HSCT. In this study, we investigated whether the single-nucleotide polymorphisms (SNPs) of the co-stimulatory genes within non-HLA regions were related to the outcomes of HSCT. The genomic DNAs of 163 patients who had acute leukemia and received HSCT and their respective donors were collected for analysis. Thirty-four SNPs located in the four co-stimulatory genes including cytotoxic T-lymphocyte associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily 4 (TNFSF4), and programmed cell death protein 1 (PDCD1) were selected to explore their relationship with the adverse outcomes after transplantation, including mortality, cytomegalovirus infection, graft-versus-host disease, and relapse. Our results revealed that nine SNPs in the CTLA4 gene, five SNPs in the PDCD1 gene, two SNPs in the TNFSF4 gene, and four SNPs in the CD28 gene were significantly associated with the occurrence of adverse outcomes post-HSCT. These SNPs may play important roles in immune response to allografts post-HSCT and can be the targets for developing strategy to identify appropriate donors.

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Section: Introductionmentioning

confidence: 99%

The Association Between Single-Nucleotide Polymorphisms of Co-Stimulatory Genes Within Non-HLA Region and the Prognosis of Leukemia Patients With Hematopoietic Stem Cell Transplantation

et al. 2021

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“…HLA shows typical haplotype characteristics according to individual ethnic groups [ 10 , 11 ]. Therefore, HLA-DQ can be predicted using HLA haplotype frequency and linkage disequilibrium (LD) data.…”

Section: Introductionmentioning

confidence: 99%

Prediction of HLA-DQ in Deceased Donors and its Clinical Significance in Kidney Transplantation

et al. 2021

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Background HLA-DQ typing in deceased donors is not mandatory in Korea. Therefore, when patients develop DQ antibodies after kidney transplantation (KT) from deceased donor, it is impossible to determine whether they are donor-specific antibodies (DSA). We developed DQ prediction programs for the HLA gene and evaluated their clinical utility. Methods Two HLA-DQ prediction programs were developed one based on Lewontin’s linkage disequilibrium (LD) and haplotype frequency and the other on an artificial neural network (ANN). Low-resolution HLA-A, -B, -DR, and -DQ typing data of 5,603 Korean patients were analyzed in terms of haplotype frequency and used to develop an ANN DQ prediction program. Predicted DQ (pDQ) genotype accuracy was analyzed using the typed DQ data of 403 patients. pDQ DSA agreement, sensitivity, specificity, and false-negative rate was evaluated using 1,970 single-antigen bead assays performed on 885 KT recipients. The clinical significance of DQ and pDQ DSA was evaluated in 411 KT recipients. Results pDQ genotype accuracies were 75.4% (LD algorithm) and 75.7% (ANN). When the second most likely pDQ (LD algorithm) was also considered, the genotype accuracy increased to 92.6%. pDQ DSA (LD algorithm) agreement, sensitivity, specificity, and falsenegative rate were 97.5%, 97.3%, 98.6%, and 2.4%, respectively. The antibody-mediated rejection treatment frequency was significantly higher in DQ or pDQ DSA-positive patients than in DQ or pDQ DSA-negative patients ( P < 0.001). Conclusions Our DQ prediction programs showed good accuracy and could aid DQ DSA detection in patients who had undergone deceased donor KT without donor HLA-DQ typing.

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Understanding population-wide haplotype frequencies of human leukocyte antigen (HLA) alleles in linkage disequilibrium is important for hematopoietic stem cell transplantation

Cited by 2 publications

References 10 publications

The Association Between Single-Nucleotide Polymorphisms of Co-Stimulatory Genes Within Non-HLA Region and the Prognosis of Leukemia Patients With Hematopoietic Stem Cell Transplantation

The Association Between Single-Nucleotide Polymorphisms of Co-Stimulatory Genes Within Non-HLA Region and the Prognosis of Leukemia Patients With Hematopoietic Stem Cell Transplantation

Prediction of HLA-DQ in Deceased Donors and its Clinical Significance in Kidney Transplantation

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