RESUMEN
The novel HLA-DPB1*14:01:15 allele differs from DPB1*14:01:01:01 by change of C > T in exon 3.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Cadenas beta de HLA-DP , Prueba de Histocompatibilidad , Donantes de Tejidos , Humanos , Cadenas beta de HLA-DP/genética , Brasil , Análisis de Secuencia de ADN/métodos , Médula Ósea , Alineación de Secuencia , Codón , Trasplante de Médula ÓseaRESUMEN
To analyse the effect of HLA-DPA1 and HLA-DPB1 allelic mismatches on the outcomes of unrelated donor haematopoietic stem cell transplantation (URD-HSCT), we collected 258 recipients with haematological disease who underwent HLA-10/10 matched URD-HSCT. HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5, -DQA1, -DPA1 and -DPB1 typing was performed for the donors and recipients using next-generation sequencing (NGS) technology. After excluding 8 cases with DQA1 or DRB3/4/5 mismatches, we included 250 cases with HLA-14/14 matching for further analysis. Our results showed that the proportion of matched DPA1 and DPB1 alleles was only 10.4% (26/250). The remaining 89.6% of donors and recipients demonstrated DPA1 or DPB1 mismatch. In the DPA1 matched and DPB1 mismatched group, accounting for 18.8% (47/250) of the cohort, DPB1*02:01/DPB1*03:01 allelic mismatches were associated with decreased 2-year OS and increased NRM. DPB1*02:02/DPB1*05:01 and DPB1*02:01/DPB1*05:01 mismatches showed no impact on outcomes. Moreover, the specific allelic mismatches observed were consistent with the DPB1 T-cell epitope (TCE) classification as permissive and non-permissive. We innovatively established an analysis method for DPA1 ~ DPB1 linkage mismatch for cases with both DPA1 and DPB1 mismatched, accounting for 70% (175/250) of the total. DPA1*02:02 ~ DPB1*05:01/DPA1*02:01 ~ DPB1*17:01 linkage mismatches were associated with lower 2-year OS, especially among AML/MDS recipients. DPA1*02:02 ~ DPB1*05:01/DPA1*01:03 ~ DPB1*02:01 linkage mismatches showed no impact on outcomes. In conclusion, applying the DPA1 ~ DPB1 linkage mismatch analysis approach can identify different types of mismatches affecting transplant outcomes and provide valuable insight for selecting optimal donors for AML/MDS and ALL recipients.
Asunto(s)
Alelos , Cadenas alfa de HLA-DP , Cadenas beta de HLA-DP , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Donante no Emparentado , Humanos , Cadenas beta de HLA-DP/genética , Trasplante de Células Madre Hematopoyéticas/métodos , Cadenas alfa de HLA-DP/genética , Masculino , Prueba de Histocompatibilidad/métodos , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Niño , Preescolar , Anciano , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/inmunologíaRESUMEN
HLA-DPB1*1553:01 differs from HLA-DPB1*09:01:01:01 by one nucleotide in exon 3.
Asunto(s)
Exones , Cadenas beta de HLA-DP , Prueba de Histocompatibilidad , Humanos , Alelos , Secuencia de Bases , Codón , Pueblos del Este de Asia , Cadenas beta de HLA-DP/genética , Alineación de Secuencia , Análisis de Secuencia de ADN/métodos , Donantes de TejidosRESUMEN
The novel HLA-DPB1*1591:01 allele was detected during the HLA typing for kidney transplantation.
Asunto(s)
Alelos , Cadenas beta de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Trasplante de Riñón , Humanos , Cadenas beta de HLA-DP/genética , Prueba de Histocompatibilidad/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Exones , Secuencia de Bases , Donantes de TejidosRESUMEN
HLA-DPB1*05:01:20 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.
Asunto(s)
Alelos , Pueblo Asiatico , Secuencia de Bases , Exones , Cadenas beta de HLA-DP , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Cadenas beta de HLA-DP/genética , Pueblo Asiatico/genética , Análisis de Secuencia de ADN/métodos , Donantes de Tejidos , Alineación de Secuencia , Codón , Pueblos del Este de AsiaRESUMEN
The novel HLA-DPB1*1437:01 and HLA-DPB1*1438:01 alleles first identified in the Chinese individuals.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Cadenas beta de HLA-DP/genéticaRESUMEN
The novel allele HLA-DPB1*1467:01 differs from HLA-DPB1*09:01:01:01 by one non-synonymous nucleotide substitution in exon 2.
Asunto(s)
Secuencia de Bases , Humanos , Alelos , Cadenas beta de HLA-DP/genética , Exones/genética , Análisis de Secuencia de ADNRESUMEN
HLA-DPB1*1500:01N differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.
Asunto(s)
Cadenas beta de HLA-DP , Nucleótidos , Humanos , Alelos , Secuencia de Bases , China , Análisis de Secuencia de ADNRESUMEN
The presence of an HLA-DPB1 nonpermissive mismatch (NPMM) by the TCE-3 model has been associated with improved survival following haploidentical donor transplantation (HIDT) using post-transplantation cyclophosphamide (PTCy). With the development of a revised model (TCE-Core) that further separates TCE-3 "group 3" alleles into "core" (C) and "noncore" (NC) alleles, a formerly permissive mismatch (PMM) resulting from group 3 alleles in both donor and recipient is now considered a C-NPMM if 1 or more of those alleles is NC. We aimed to study the additional effect of HLA-DPB1 C-NPMM according to the TCE-Core algorithm, as well as the directional vector of the mismatch, on outcomes following HIDT. To this end, we analyzed 242 consecutive HIDT recipients with acute leukemia or myelodysplastic syndrome who underwent transplantation between 2005 and 2021 (median age, 51 years; range, 19 to 80 years). The median follow-up was 62 months (range, 23 to 199 months). Of the 136 HIDTs classified as PMM by TCE-3, 73 were reclassified as a C-NPMM by the TCE-Core algorithm, of which 36 were in the graft-versus host (GVH) vector (37 were host-versus-graft [HVG] only). Given comparable survival between conventional NPMM and C-NPMM, GVH/bidirectional were analyzed together (nonpermissive). HVG-only C-NPMM were combined with HLA-DPB1-matched and PMM (permissive) because of similar outcomes. The presence of a TCE-Core-defined nonpermissive HLA-DP mismatch resulted in superior 5-year overall survival (OS) (66% versus 47%) and disease-free survival (DFS) (60% versus 43%). Compared to the conventional TCE-3 algorithm, TCE-Core identified a higher percentage of nonpermissive transplants (38% versus 23%) and better discriminated outcomes between nonpermissive and permissive status, with a larger difference in survival outcomes using TCE-Core compared to TCE-3 (OS Δ, 18.3% versus 12.7%; DFS Δ, 16.5% versus 8.5%). In multivariable analysis (MVA), a nonpermissive TCE-Core mismatch led to improved OS (hazard ratio [HR], .54; P = .003) and DFS (HR, .62; P = .013), largely due to decreased relapse risk (HR, .63; P = .049). In contrast, nonrelapse mortality (NRM) and graft-versus-host disease (GVHD) outcomes were not significantly impacted. In summary, the presence of nonpermissive TCE-Core HLA-DP mismatch strongly predicts survival following PTCy-based HIDT, owing to a reduction in relapse risk without a corresponding increase in GVHD or NRM. As a donor selection tool, TCE-Core appears to better discriminate HIDT outcomes while at the same time identifying a larger percentage of the potential donor pool.
Asunto(s)
Recurrencia , Trasplante Haploidéntico , Humanos , Persona de Mediana Edad , Adulto , Femenino , Masculino , Anciano , Adulto Joven , Cadenas beta de HLA-DP/genética , Cadenas beta de HLA-DP/metabolismo , Anciano de 80 o más Años , Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos/terapia , Síndromes Mielodisplásicos/mortalidad , Alelos , Enfermedad Injerto contra Huésped/inmunologíaRESUMEN
The novel HLA-DPB1*1449:01N allele differs from HLA-DPB1*16:01:01:01 by a nucleotide at codon 92 in exon 2.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Exones/genética , Cadenas beta de HLA-DP/genéticaRESUMEN
HLA-DPB1*05:01:21 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.
Asunto(s)
Cadenas beta de HLA-DP , Nucleótidos , Humanos , Alelos , Secuencia de Bases , ChinaRESUMEN
HLA-DPB1*03:01:29 differs from HLA-DPB1*03:01:01:01 by one nucleotide in exon 2.
Asunto(s)
Cadenas beta de HLA-DP , Nucleótidos , Humanos , Alelos , Análisis de Secuencia de ADN , ChinaRESUMEN
HLA-DPB1*1584:01 differs from HLA-DPB1*104:01:01:03 by one nucleotide substitution in exon 2.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Secuencia de Bases , Alelos , Cadenas beta de HLA-DP/genéticaRESUMEN
Objective: To evaluate the risk prediction and assessment function of HLA-DPB1 T-cell epitope (TCE) model and expression model in human leukocyte antigen (HLA)-matched unrelated hematopoietic stem cell transplantation (MUD-HSCT) with HLA-DPB1 mismatching. Methods: A total of 364 (182 pairs) potential MUD-HSCT donors and recipients confirmed by HLA high-resolution typing in Shaanxi Blood Center from 2016 to 2019 were analyzed retrospectively. Of the 182 recipients, there were 121 males and 61 females with an average age of (26.3±14.2) years. Of the 182 donors, there were 148 males and 34 females with an average age of (33.7±7.5) years. Polymerase chain reaction-sequence-based typing (PCR-SBT), next-generation sequencing (NGS) and polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSO) based on LABScan®3D platform were used for high-resolution typing of HLA-A, B, C, DRB1, DQB1, DPB1 gene, and PCR-SBT was used for single nucleotide polymorphism (SNP) typing. TCE model and expression model were used to predict and evaluate the HLA-DPB1 mismatch pattern and acute graft-versus-host-disease (aGVHD) risk. Results: A total of 26 HLA-DPB1 alleles and their 3'-UTR rs9277534 SNP genotypes were detected in this study population, and two new alleles HLA-DPB1*1052â¶01 and HLA-DPB1*1119â¶01 were found and officially named. The overall mismatch rate of HLA-DPB1 in MUD-HSCT donors and recipients was 90.66% (165/182). In TCE model, the HLA-DPB1 mismatch rates of permissible mismatch (PM) and non-permissible mismatch (non-PM) were 47.80% (87/182) and 42.86% (78/182), respectively. The non-PM in GvH direction was 13.73% (25/182), and which in HvG direction was 29.12% (53/182). A total of 73 pairs of donors and recipients in TCE model met the evaluation criteria of expression model. Among of TCE PM group, recipient DP5 mismatches accounted for 34.25% (25/73) were predicted as aGVHD high risk according to expression model. For the TCE non-PM group, both the recipient DP2 mismatches of 6.85% (5/73) and recipient DP5 mismatches of 10.86% (8/73) were predicted to be at high risk for aGVHD. Risk prediction by TCE model and expression model was 27.27% concordant and 16.97% unconcordant. Conclusions: TCE model and expression model are effective tools to predict aGVHD risk of MUD-HSCT. Comprehensive application of the two models is helpful to the hierarchical assessment of HSCT risk.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Masculino , Femenino , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Epítopos de Linfocito T/genética , Estudios Retrospectivos , Cadenas beta de HLA-DP/genética , Donante no Emparentado , Enfermedad Injerto contra Huésped/genéticaRESUMEN
Identification of four new HLA alleles (B*27:265, B*35:569, DRB1*08:117, and DPB1*1435:01) in Brazilian bone marrow donors.
Asunto(s)
Antígenos HLA-B , Humanos , Frecuencia de los Genes , Alelos , Cadenas beta de HLA-DP/genética , Cadenas HLA-DRB1/genética , Antígenos HLA-B/genéticaRESUMEN
HLA-DPB1*1550:01 differs from HLA-DPB1*02:02:01:01 by one nucleotide in exon 2.
Asunto(s)
Cadenas beta de HLA-DP , Nucleótidos , Humanos , Alelos , Secuencia de Bases , ChinaRESUMEN
Characterization of two novel HLA-DPB1 alleles: HLA-DPB1*1069:01, and DPB1*1072:01 containing non-synonymous nucleotide substitutions.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Nucleótidos , Humanos , Alelos , Cadenas beta de HLA-DP/genéticaRESUMEN
We determined the genetic association between specific human leucocyte antigen (HLA) loci and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Our results showed that autoimmune GFAP astrocytopathy was associated with HLA-A*3303 (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.32-3.06, p = 0.00072, padj. = 0.046) and HLA-DBP1*0501 (OR = 0.51, 95% CI = 0.36-0.71, p = 0.000048, padj. = 0.0062). Moreover, HLA-A*3303 carriers with the disease had a longer hospital stay (p = 0.0005) than non-carriers. This study for the first time provides evidence for a role of genetic factor in the development of autoimmune GFAP astrocytopathy. ANN NEUROL 2024;95:901-906.
Asunto(s)
Astrocitos , Proteína Ácida Fibrilar de la Glía , Antígenos HLA-A , Cadenas beta de HLA-DP , Humanos , Proteína Ácida Fibrilar de la Glía/genética , Masculino , Femenino , Persona de Mediana Edad , Cadenas beta de HLA-DP/genética , Adulto , Antígenos HLA-A/genética , Astrocitos/metabolismo , Astrocitos/patología , AncianoRESUMEN
HLA-DPB1*1516:01 differs from HLA-DPB1*1229:01 by seven nucleotide substitutions in exon 3.
Asunto(s)
Secuencia de Bases , Humanos , Alelos , Cadenas beta de HLA-DP/genética , Exones/genéticaRESUMEN
Two novel alleles, HLA-G*01:04:09 and HLA-DPB1*04:01:01:136, were identified in a single healthy individual.