HLA最新文献

This study investigates the HLA allele diversity in Brazil, a reflection of the country's unique history of population admixture. The international comparison of findings emphasises the importance of incorporating underrepresented populations into global HLA databases. We present a comprehensive analysis of HLA alleles within the Brazilian population, utilising high-resolution sequencing data from 298,000 unrelated haematopoietic stem cell volunteer donors registered with the Brazilian Bone Marrow Donor Registry (REDOME). Our research encompasses donors from all regions of Brazil, identifying HLA alleles that are catalogued as common, intermediate or well-documented (CIWD Version 3.0). We evaluated the alleles of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1. At a two-field resolution, we identified 1969 alleles: 418 were classified as common, 358 as intermediate and 1193 as non-CIWD in Brazil. Notably, we report HLA alleles that, while not classified as common or intermediate in the CIWD 3.0 catalogue, are prevalent within the Brazilian population. A detailed list of alleles from the registry, presented at a two-field resolution and supplemented with grouped ARD levels, including three- or four-field resolution when available, serves as an essential reference for HLA typing frequencies specific to the Brazilian population.

HLA-B*38:121 differs from HLA-B*38:01:01:01 by one nucleotide substitution in codon 106 in exon 3.

Identification of four novel HLA alleles, HLA-C*03:09:02:01, -C*07:04:32, -C*07:1152, and -C*08:300, in Brazilian individuals.

The US 2014 kidney allocation system (KAS) allows ABO A₂ donor kidneys to be transplanted into ABO B candidates, thereby broadening the donor pool for a traditionally disadvantaged population. Safely transplanting these patients relies heavily on two components: (1) recipient ABO antibody titres and (2) ABO A subtyping of the donor. While lectin-based serological methods remain the gold standard for ABO typing, recent data show ABO molecular genotyping is a more reliable approach to accurately assign the A₂ subtype. ABO titres were performed using Ortho Diagnostics gel cards using haemagglutination by both antiglobulin-enhanced and dithiothreitol methods. ABO genotyping was performed using innotrain diagnostiks Real-Time PCR. Here, we present two cases where ABO lectin testing incorrectly identified the donors as ABO A₂ and A₂B instead of A₁ and A₁B. Consequently, the transplants proceeded but had deleterious outcomes. These two cases support the concept that ABO genotyping by molecular methodology should be mandatory to confirm the A₂ donor subtype when transplanting kidneys from deceased donors into ABO B candidates on the waitlist and for virtual crossmatching (VXM) donors being considered for transplantation into ABO B and O recipients.

The exposure of cancer neoantigens to the patient's immune system by the HLA system sustains immune surveillance and shapes tumour clonal evolution. In acute myeloid leukaemia (AML), the mutation of Nucleophosmin 1 (NPM1) at exon 12 represents a driver mutation, raising a set of highly immunogenic peptides. Whereas the phenomenon of HLA loss is a mechanism of immune escape broadly described in allogeneic haematopoietic stem cell transplantation, less is known about this phenomenon at leukaemia diagnosis. In this study, we present a case of a 47-year-old patient with de novo NPM1-positive AML characterised by HLA loss at diagnosis due to copy neutral number loss of heterozygosity in leukaemic blasts. In silico analyses showed a high affinity of all the lost HLA allotypes for the mutated NPM1-derived tumour neopeptides, suggesting that the selective HLA loss was a relevant mechanism for blast escape from autologous T lymphocyte immunosurveillance. The HLA loss did not lead to any predicted missing ligand for educated natural killer (NK) cells expressing inhibitory killer immunoglobulin-like receptors (KIRs) for self-HLA allotypes, thus not affecting NK-mediated immunosurveillance. The present case represents a model of a ‘perfect crime’ by immunological escape of leukaemic blasts and supports mutated NPM1-derived neopeptides as an attractive target for AML immunotherapy.

The HLA-DQB1*06:524 allele differs from HLA-DQB1*06:02:43 by one nucleotide substitution in codon 57 in exon 2.

Genomic sequence of HLA-B*14:01:01:12, -B*15:01:01:67, -B*35:01:01:90, -B*35:03:01:38, -B*35:31:01:02, -B*41:01:01:09, -B*44:02:01:85 alleles.

HLA-DQB1*03:572 differs from DQB1*03:01:01:01 by one nucleotide substitution at position 208G>T in exon 2.

HLA-A*32:01:62 differs from HLA-A*32:01:01:01 by one nucleotide substitution in codon 291 in exon 5.

HLA-DRB1*13:01:44 differs from HLA-DRB1*13:01:01:01 by one nucleotide substitution in codon 180 in exon 3.