RESUMEN
HLA-DPA1*02:139 and -DPA1*02:140N, two novel HLA-DPA1 alleles detected by next-generation sequencing.
Asunto(s)
Alelos , Exones , Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Cadenas alfa de HLA-DP/genética , Cadenas alfa de HLA-DP/inmunología , Prueba de Histocompatibilidad , Secuencia de Bases , Análisis de Secuencia de ADN , CodónRESUMEN
HLA-DPA1*01:12:03 differs from HLA-DPA1*01:12:01 by one nucleotide substitution in codon 204 in exon 4.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Cadenas alfa de HLA-DP , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Cadenas alfa de HLA-DP/genética , Cadenas alfa de HLA-DP/inmunología , Prueba de Histocompatibilidad/métodos , Análisis de Secuencia de ADN/métodos , Codón , Alineación de SecuenciaRESUMEN
HLA-DPA1*02:134, a novel HLA class II allele detected by next-generation sequencing.
Asunto(s)
Alelos , Exones , Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Cadenas alfa de HLA-DP/genética , Prueba de Histocompatibilidad/métodos , CodónRESUMEN
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
The novel HLA-DPA1*01:195 allele differs from HLA-DPA1*01:03:01:01 by one nucleotide substitution in exon 4.
Asunto(s)
Alelos , Exones , Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Humanos , Cadenas alfa de HLA-DP/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Prueba de Histocompatibilidad/métodos , Secuencia de Bases , Análisis de Secuencia de ADN/métodos , Polimorfismo de Nucleótido Simple , Alineación de SecuenciaRESUMEN
Genomic sequence of HLA-DPA1*01:03:01:73, -DPA1*01:03:01:80, DPA1*01:03:01:82, -DPA1*01:155:01:02, -DPA1*02:02:02:16 alleles in Spanish individuals.
Asunto(s)
Alelos , Cadenas alfa de HLA-DP , Humanos , Cadenas alfa de HLA-DP/genética , Exones , España , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Secuencia de Bases , Alineación de SecuenciaRESUMEN
Aim: Inherent variations in human leukocyte antigen (HLA) alleles have been revealed epidemiologically to influence the development of autoimmune diseases. HLA alleles may thus also be associated with the development of immune-related adverse events (irAEs), such as thyroid irAE.Materials & methods: In this case-control study, 71 cancer patients who received immune checkpoint inhibitors were enrolled and HLA-genotyped and the frequency of HLA alleles was compared.Results: A*26:01, DPA1*01:03 and DPB1*02:01 were significantly more frequent in patients with thyroid irAE than in patients without any irAEs (35.0 vs 3.2% [p = 0.004], 80.0 vs 45.2% [p = 0.020] and 55.0 vs 25.8% [p = 0.044], respectively).Conclusion: A*26:01, DPA1*01:03 and DPB1*02:01 appear to be associated with thyroid irAE.
Everyone has a unique combination of human leukocyte antigens (HLAs) in their body that help the immune system identify threats. HLAs were named from the fact that they were first identified on the surface of human leukocytes. Afterward, HLAs were also found on all human cells. HLAs present antigens to immune cells. These HLAs also influence how the immune system attacks cancer cells. Immune checkpoint inhibitors are drugs that can help the immune system fight cancer, but they sometimes cause severe adverse events. In this study, we investigated whether specific HLA genes are related to the development of an adverse event that affects the thyroid in cancer patients treated with immune checkpoint inhibitors. We found an association between three HLA genes (A*26:01, DPA1*01:03 and DPB1*02:01) and the development of the thyroid adverse event. However, larger studies are needed to confirm and generalize these initial exploratory findings.
Asunto(s)
Alelos , Humanos , Masculino , Femenino , Estudios de Casos y Controles , Persona de Mediana Edad , Neoplasias/inmunología , Neoplasias/genética , Anciano , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Adulto , Glándula Tiroides/inmunología , Antígenos HLA/genética , Antígenos HLA/inmunología , Genotipo , Cadenas alfa de HLA-DP/genética , Cadenas alfa de HLA-DP/efectos adversos , Cadenas beta de HLA-DP/genética , Cadenas beta de HLA-DP/inmunología , Predisposición Genética a la Enfermedad , Frecuencia de los GenesRESUMEN
The novel HLA-DPA1*02:07:04 allele was detected during the HLA typing for kidney transplantation.
Asunto(s)
Alelos , Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Trasplante de Riñón , Humanos , Cadenas alfa de HLA-DP/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Prueba de Histocompatibilidad/métodos , ExonesRESUMEN
HLA-DPA1*02:86 differs from HLA-DPA1*02:01:01 by a single nucleotide substitution at position 680 C > A in exon 4.
Asunto(s)
Alelos , Exones , Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Humanos , Cadenas alfa de HLA-DP/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Prueba de Histocompatibilidad/métodos , Polimorfismo de Nucleótido Simple , Secuencia de Bases , Análisis de Secuencia de ADN/métodosRESUMEN
The new HLA-DPA1*01:182 allele differs from HLA-DPA1*01:03:01:04 by a single mismatch in exon 4.
Asunto(s)
Médula Ósea , Cadenas alfa de HLA-DP , Humanos , Alelos , Brasil , Prueba de HistocompatibilidadRESUMEN
HLA-DPA1*02:117 differs from HLA-DPA1*02:02:02:01 by one nucleotide in exon 2.
Asunto(s)
Cadenas alfa de HLA-DP , Nucleótidos , Humanos , Alelos , Cadenas alfa de HLA-DP/genética , China , Análisis de Secuencia de ADNRESUMEN
The novel HLA-DPA1*02:02:15 allele differs from HLA-DPA1*02:02:02:01 by one nucleotide substitution in exon 1.
Asunto(s)
Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Prueba de Histocompatibilidad , Cadenas alfa de HLA-DP/genéticaRESUMEN
HLA-DPA1*02:124 differs from HLA-DRB1*02:02:02:01 by one nucleotide substitution in codon 5 in exon 2.
Asunto(s)
Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Cadenas alfa de HLA-DP/genética , República de CoreaRESUMEN
HLA-DPA1*02:01:25 differs from DPA1*02:01:01:02 by a synonymous transition in exon 2.
Asunto(s)
Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Cadenas alfa de HLA-DP/genética , Exones/genéticaRESUMEN
Seven different single nucleotide substitutions in non-coding regions gave rise to novel HLA-DPA1*01:03:01 variants.
Asunto(s)
Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Cadenas alfa de HLA-DP/genética , Prueba de HistocompatibilidadRESUMEN
HLA-DPA1*02:122 differs from HLA-DPA1*02:01:01:02 by one nucleotide substitution in codon 78 in exon 2.
Asunto(s)
Cadenas alfa de HLA-DP , Humanos , Alelos , Alineación de Secuencia , Prueba de Histocompatibilidad , Cadenas alfa de HLA-DP/genética , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: Primary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring liver transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind the activating NK-cell receptor NKp44, we investigated the role of HLA-DP/NKp44-interactions in PSC. DESIGN: Liver tissue, intrahepatic and peripheral blood lymphocytes of individuals with PSC and control individuals were characterised using flow cytometry, immunohistochemical and immunofluorescence analyses. HLA-DPA1 and HLA-DPB1 imputation and association analyses were performed in 3408 individuals with PSC and 34 213 controls. NK cell activation on NKp44/HLA-DP interactions was assessed in vitro using plate-bound HLA-DP molecules and HLA-DPB wildtype versus knock-out human cholangiocyte organoids. RESULTS: NKp44+NK cells were enriched in livers, and intrahepatic bile ducts of individuals with PSC showed higher expression of HLA-DP. HLA-DP haplotype analysis revealed a highly elevated PSC risk for HLA-DPA1*02:01~B1*01:01 (OR 1.99, p=6.7×10-50). Primary NKp44+NK cells exhibited significantly higher degranulation in response to plate-bound HLA-DPA1*02:01-DPB1*01:01 compared with control HLA-DP molecules, which were inhibited by anti-NKp44-blocking. Human cholangiocyte organoids expressing HLA-DPA1*02:01-DPB1*01:01 after IFN-γ-exposure demonstrated significantly increased binding to NKp44-Fc constructs compared with unstimulated controls. Importantly, HLA-DPA1*02:01-DPB1*01:01-expressing organoids increased degranulation of NKp44+NK cells compared with HLA-DPB1-KO organoids. CONCLUSION: Our studies identify a novel PSC risk haplotype HLA-DP A1*02:01~DPB1*01:01 and provide clinical and functional data implicating NKp44+NK cells that recognise HLA-DPA1*02:01-DPB1*01:01 expressed on cholangiocytes in PSC pathogenesis.
Asunto(s)
Colangitis Esclerosante , Humanos , Haplotipos , Colangitis Esclerosante/genética , Cadenas alfa de HLA-DP/genética , Células Asesinas NaturalesRESUMEN
The novel HLA-DPA1*01:130 allele differs from HLA-DPA1*01:03:01:03 by one nucleotide substitution in Exon 3.
Asunto(s)
Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Prueba de Histocompatibilidad , Cadenas alfa de HLA-DP/genéticaRESUMEN
HLA-DPA1*01:03:51 differs from HLA-DPA1*01:03:01:01 by one nucleotide substitution in codon 146 in exon 3.
Asunto(s)
Cadenas alfa de HLA-DP , Humanos , Alelos , Alineación de Secuencia , Prueba de Histocompatibilidad , Cadenas alfa de HLA-DP/genéticaRESUMEN
The novel HLA-DPA1*01:149 allele differs from HLA-DPA1*01:03:01:05 by one nucleotide substitution in exon 2.
