ABSTRACT
HLA-DQB1*06:466 differs from HLA-DQB1*06:01:01:01 by a single nucleotide substitution at position 571GâA.
Subject(s)
Alleles , Asian People , Blood Donors , Exons , Fetal Blood , HLA-DQ beta-Chains , High-Throughput Nucleotide Sequencing , Humans , HLA-DQ beta-Chains/genetics , High-Throughput Nucleotide Sequencing/methods , Asian People/genetics , Histocompatibility Testing/methods , Polymorphism, Single Nucleotide , Base Sequence , Sequence Analysis, DNA/methods , East Asian PeopleABSTRACT
HLA-C*03:620 differs from the HLA-C*03:04:01:02 allele by one nucleotide substitution in the exon 3.
Subject(s)
Alleles , Asian People , Base Sequence , Exons , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Asian People/genetics , Sequence Analysis, DNA/methods , Codon , Sequence Alignment , Polymorphism, Single Nucleotide , East Asian PeopleABSTRACT
HLA-DPB1*05:01:20 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.
Subject(s)
Alleles , Asian People , Base Sequence , Exons , HLA-DP beta-Chains , Histocompatibility Testing , Sequence Analysis, DNA , Humans , HLA-DP beta-Chains/genetics , Asian People/genetics , Sequence Analysis, DNA/methods , Tissue Donors , Sequence Alignment , Codon , East Asian PeopleABSTRACT
HLA-B*15:659 differs from HLA-B*15:02:01:01 by one nucleotide in exon 2.
Subject(s)
Alleles , Asian People , Base Sequence , Exons , Histocompatibility Testing , Sequence Analysis, DNA , Humans , Asian People/genetics , Sequence Analysis, DNA/methods , HLA-B15 Antigen/genetics , HLA-B15 Antigen/immunology , Sequence Alignment , Codon , Tissue Donors , East Asian PeopleABSTRACT
Genomic full-length sequence of HLA-B*37:46 was identified by a group-specific sequencing approach in a Chinese individual.
Subject(s)
Alleles , Asian People , HLA-B Antigens , Histocompatibility Testing , Sequence Analysis, DNA , Humans , HLA-B Antigens/genetics , Sequence Analysis, DNA/methods , Histocompatibility Testing/methods , Asian People/genetics , Exons , Base SequenceABSTRACT
Two different single nucleotide substitutions in intron 2 give rise to novel HLA-DQB1*03:02:01 alleles.
Subject(s)
Alleles , HLA-DQ beta-Chains , Introns , Humans , Histocompatibility Testing , HLA-DQ beta-Chains/genetics , Polymorphism, Single NucleotideABSTRACT
Compared with HLA-DRB1*12:02, the alleles HLA-DRB1*12:92 and HLA-DRB1*12:101 each show one nucleotide substitution respectively.
Subject(s)
Alleles , HLA-DRB1 Chains , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Humans , HLA-DRB1 Chains/genetics , High-Throughput Nucleotide Sequencing/methods , Histocompatibility Testing/methods , Exons , Polymorphism, Single Nucleotide , Base Sequence , Sequence Analysis, DNA/methodsABSTRACT
Introduction: Polymorphisms in the KIR and HLA genes contribute to the diversity of the NK cell repertoire. Extrinsic factors also play a role in modifying this repertoire. The best example is cytomegalovirus, which promotes the expansion of memory-like NK cells. However, the mechanisms governing this phenotypic structure are poorly understood. Furthermore, the influence of age and sex has been understudied. Methods: In this study, we examined these parameters in a cohort of 200 healthy volunteer blood donors, focusing on the major inhibitory KIR receptors and CD94/NKG2A, as well as the differentiation marker CD57 and the memory-like population marker NKG2C. Flow cytometry and two joint analyses, unsupervised and semi-supervised, helped define the impact of various intrinsic and extrinsic markers on the phenotypic structure of the NK cell repertoire. Results: In the KIR NK cell compartment, the KIR3DL1 gene is crucial, as unexpressed alleles lead to a repertoire dominated by KIR2D interacting only with HLA-C ligands, whereas an expressed KIR3DL1 gene allows for a greater diversity of NK cell subpopulations interacting with all HLA class I ligands. KIR2DL2 subsequently favors the KIR2D NK cell repertoire specific to C1/C2 ligands, whereas its absence promotes the expression of KIR2DL1 specific to the C2 ligand. The C2C2Bw4+ environment, marked by strong -21T motifs, favors the expansion of the NK cell population expressing only CD57, whereas the absence of HLA-A3/A11 ligands favors the population expressing only NKG2A, a population highly represented within the repertoire. The AA KIR genotype favors NK cell populations without KIR and NKG2A receptors, whereas the KIR B+ genotypes favor populations expressing KIR and NKG2A. Interestingly, we showed that women have a repertoire enriched in CD57- NK cell populations, while men have more CD57+ NK cell subpopulations. Discussion: Overall, our data demonstrate that the phenotypic structure of the NK cell repertoire follows well-defined genetic rules and that immunological history, sex, and age contribute to shaping this NK cell diversity. These elements can contribute to the better selection of hematopoietic stem cell donors and the definition of allogeneic NK cells for cell engineering in NK cell-based immunotherapy approaches.cters are displayed correctly.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Genotype , Killer Cells, Natural , Receptors, KIR , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Female , Male , Adult , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/genetics , Cytomegalovirus/immunology , Receptors, KIR/genetics , Middle Aged , Sex Factors , Age Factors , CD57 Antigens , Histocompatibility Testing , Young Adult , NK Cell Lectin-Like Receptor Subfamily C/genetics , HLA Antigens/genetics , HLA Antigens/immunology , Aged , Receptors, KIR3DL1/geneticsABSTRACT
The novel HLA-A*02:1140 allele, first described in a potential bone marrow donor from Brazil.
Subject(s)
Alleles , HLA-A2 Antigen , Humans , Brazil , HLA-A2 Antigen/genetics , HLA-A2 Antigen/immunology , Histocompatibility Testing , Exons , Tissue Donors , Base Sequence , Sequence Analysis, DNA/methods , Sequence AlignmentABSTRACT
Nucleotide substitution in codon 238 of HLA-C*12:02:02:01 results in a novel allele, HLA-C*12:02:53.
Subject(s)
Alleles , Base Sequence , Codon , Exons , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Taiwan , Sequence Analysis, DNA , Asian People/genetics , Sequence Alignment , Polymorphism, Single Nucleotide , Amino Acid SubstitutionABSTRACT
HLA-DQA1*02:32 differs from DQA1*02:01:01 by one nucleotide substitution in codon 210 in exon 4.
Subject(s)
Alleles , Exons , HLA-DQ alpha-Chains , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Humans , HLA-DQ alpha-Chains/genetics , High-Throughput Nucleotide Sequencing/methods , Histocompatibility Testing/methods , Base Sequence , Codon , Sequence Analysis, DNA/methodsABSTRACT
The novel HLA-C*15:274 allele, first described in a potential bone marrow donor from Brazil.
Subject(s)
Alleles , Exons , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Histocompatibility Testing/methods , Sequence Analysis, DNA/methods , Tissue Donors , Brazil , High-Throughput Nucleotide Sequencing/methods , Base SequenceABSTRACT
HLA-DRB4*01:01:12 differs from HLA-DRB4*01:01:01:01 by one nucleotide substitution in codon 175 in exon 3.
Subject(s)
Alleles , Base Sequence , Exons , HLA-DRB4 Chains , Histocompatibility Testing , Sequence Analysis, DNA , Humans , Histocompatibility Testing/methods , Sequence Analysis, DNA/methods , HLA-DRB4 Chains/genetics , Codon , Sequence AlignmentABSTRACT
HLA-B*15:02:15 differs from HLA-B*15:02:01:01 by one nucleotide in exon 2.
Subject(s)
Exons , HLA-B15 Antigen , Histocompatibility Testing , Humans , Alleles , Base Sequence , Codon , East Asian People , HLA-B15 Antigen/genetics , HLA-B15 Antigen/immunology , Sequence Alignment , Sequence Analysis, DNA/methodsABSTRACT
The novel HLA-DPA1*02:07:04 allele was detected during the HLA typing for kidney transplantation.
Subject(s)
Alleles , HLA-DP alpha-Chains , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Kidney Transplantation , Humans , HLA-DP alpha-Chains/genetics , High-Throughput Nucleotide Sequencing/methods , Histocompatibility Testing/methods , ExonsABSTRACT
BACKGROUND: Optimizing graft survival and diminishing human leukocyte antigen (HLA) sensitization are essential for pediatric kidney transplant recipients. More precise HLA matching predicting epitope mismatches could reduce alloreactivity. We investigated the association of predicted HLA B- and T-cell molecular mismatches with the formation of de novo donor-specific antibodies, HLA antibodies, rejection, and graft survival. METHODS: Forty-nine pediatric kidney transplant recipients transplanted from 2009 to 2020 were retrospectively studied. Donors and recipients were high-resolution HLA typed, and recipients were screened for HLA antibodies posttransplant. HLA-EMMA (HLA Epitope MisMatch Algorithm) and PIRCHE-II (Predicted Indirectly ReCognizable HLA Epitopes) predicted the molecular mismatches. The association of molecular mismatches and the end-points was explored with logistic regression. RESULTS: Five recipients (11%) developed de novo donor-specific antibodies. All five had de novo donor-specific antibodies against HLA class II, with four having HLA-DQ antibodies. We found no associations between PIRCHE-II or HLA-EMMA with de novo donor-specific antibodies, HLA sensitization, graft loss, or rejection. However, we did see a tendency towards an increased odds ratio in PIRCHE-II predicting de novo donor-specific antibodies formation, with an odds ratio of 1.12 (95% CI: 0.99; 1.28) on HLA class II. CONCLUSION: While the study revealed no significant associations between the number of molecular mismatches and outcomes, a notable trend was observed - indicating a reduced risk of dnDSA formation with improved molecular match. It is important to acknowledge, however, that the modest population size and limited observed outcomes preclude us from making definitive conclusions.
Subject(s)
Graft Rejection , Graft Survival , HLA Antigens , Histocompatibility Testing , Kidney Transplantation , T-Lymphocytes , Humans , Graft Rejection/immunology , Child , Graft Survival/immunology , Female , Male , Retrospective Studies , Adolescent , Child, Preschool , HLA Antigens/immunology , T-Lymphocytes/immunology , Isoantibodies/immunology , Isoantibodies/blood , Infant , HLA-B Antigens/immunology , B-Lymphocytes/immunologyABSTRACT
HLA matching in solid organ transplant is performed with the aim of assessing immunologic compatibility in order to avoid hyperacute rejection and assess the risk of future rejection events. Molecular mismatch algorithms are intended to improve granularity in histocompatibility assessment and risk stratification. PIRCHE-II uses HLA genotyping to predict indirectly presented mismatched donor HLA peptides, though most clinical validation studies rely on imputing high resolution (HR) genotypes from low resolution (LR) typing data. We hypothesized that use of bona fide HR typing could overcome limitations in imputation, improving accuracy and predictive ability for donor-specific antibody development and acute rejection. We performed a retrospective analysis of adult and pediatric kidney transplant donor/recipient pairs (N = 419) with HR typing and compared the use of imputed LR genotyping verses HR genotyping for PIRCHE-II analysis and outcomes. Imputation success was highly dependent on the reference population used, as using historic Caucasian reference populations resulted in 10 % of pairs with unsuccessful imputation while multiethnic reference populations improved successful imputation with only 1 % unable to be imputed. Comparing PIRCHE-II analysis with HR and LR genotyping produced notably different results, with 20 % of patients discrepantly classified to immunologic risk groups. These data emphasize the importance of using multiethnic reference panels when performing imputation and indicate HR HLA genotyping has clinically meaningful benefit for PIRCHE-II analysis compared to imputed LR typing.
Subject(s)
Genotype , Graft Rejection , HLA Antigens , Histocompatibility Testing , Kidney Transplantation , Humans , HLA Antigens/genetics , HLA Antigens/immunology , Histocompatibility Testing/methods , Graft Rejection/genetics , Graft Rejection/immunology , Retrospective Studies , Adult , Female , Male , Child , Middle Aged , Adolescent , Histocompatibility , Genotyping Techniques/methods , AlgorithmsSubject(s)
Hematopoietic Stem Cell Transplantation , Siblings , Unrelated Donors , Humans , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/mortality , Adult , Middle Aged , Female , Male , HLA Antigens/immunology , Young Adult , Age Factors , Adolescent , Histocompatibility Testing , Survival Rate , AgedABSTRACT
The novel HLA-C*08:275 allele, first described in a potential bone marrow donor from Brazil.