RESUMO
Antibody identification by a bead array assay in a kidney patient revealed several HLA-specific antibodies including one directed against the HLA-B7 antigen. Low-resolution typing of the patient indicated the presence of an HLA-B*07 allele. To rule out an HLA-specific autoantibody the HLA-typing of the patient was further refined by nucleotide sequencing on a next-generation sequencing platform and eventually showed an HLA-B*39:01:01:03 and HLA-B*07:181N genotype. Thereby the allospecific nature of the antibody was proven. The HLA-B7-specific antibody could be explained by an immunization during the first kidney-transplantation in 1996 with an HLA-B*07 positive donor. When assessing the plausibility of antibodies, the presence of nonexpressed alleles should be taken into consideration.
Assuntos
Alelos , Antígeno HLA-B39/genética , Antígeno HLA-B7/genética , Isoanticorpos/genética , Transplante de Rim/métodos , Transplantados , Adulto , Sequência de Bases , Feminino , Expressão Gênica , Genótipo , Antígeno HLA-B39/imunologia , Antígeno HLA-B7/imunologia , Sequenciamento de Nucleotídeos em Larga Escala , Teste de Histocompatibilidade , Humanos , Reação em Cadeia da Polimerase , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Alinhamento de Sequência , Análise de Sequência de DNA , Doadores de Tecidos , Transplante HomólogoRESUMO
Full-length sequences of HLA-B*39:05:01 and B*39:38Q , confirmed by cloning and sequencing in Chinese donors.
Assuntos
Alelos , Sequência de Bases , Éxons , Antígeno HLA-B39/genética , Mutagênese Insercional , Deleção de Sequência , Povo Asiático , Clonagem Molecular , Códon/química , Expressão Gênica , Genótipo , Antígeno HLA-B39/imunologia , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Íntrons , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNA , Doadores de TecidosRESUMO
BACKGROUND: We analysed the previously reported association of the HLA-A*24:02, B*18 and B*39 alleles with type 1 diabetes and diabetes associated autoimmunity in the Finnish population applying HLA-DR/DQ stratification. MATERIALS & METHODS: Haplotype transmission was analysed in 2424 nuclear families from the Finnish Paediatric Diabetes Register. Survival analysis was applied to study the development of islet autoantibodies and further progression to clinical diabetes in the prospective follow-up cohort from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study. The subjects were genotyped for specific HLA class I alleles by sequence-specific hybridization using lanthanide labelled nucleotide probes. RESULTS: The HLA-B*39:06 allele was found almost exclusively on the (DR8)-DQB1*04 haplotype in which its presence changed the disease risk status of the whole haplotype from neutral to predisposing. The HLA-A*24:02 and the B*39:01 alleles increased the diabetes-associated risk of the DRB1*04:04-DQA1*03-DQB1*03:02 haplotype but the alleles were in linkage disequilibrium and no independent effect could be detected. Within the DIPP cohort, neither the A*24:02 nor the B*39:01 allele were associated with seroconversion but were in contrast associated with increased progression from seroconversion to clinical disease. DISCUSSION & CONCLUSIONS: The independent predisposing effect of the HLA-B*39:06 allele with type 1 diabetes was confirmed in the Finnish population but the association of the A*24:02 and B*39:01 alleles remained inconclusive whilst both A*24:02 and B*39:01 affected the progression rate from seroconversion to autoantibody positivity to overt type 1 diabetes.
Assuntos
Autoanticorpos/biossíntese , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Antígeno HLA-A24/genética , Antígeno HLA-B39/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Adulto , Alelos , Criança , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Progressão da Doença , Família , Feminino , Finlândia , Expressão Gênica , Antígeno HLA-A24/imunologia , Antígeno HLA-B39/imunologia , Antígenos HLA-DQ/imunologia , Antígenos HLA-DR/imunologia , Haplótipos , Humanos , Estimativa de Kaplan-Meier , Desequilíbrio de Ligação , Masculino , Prognóstico , Estudos ProspectivosRESUMO
The new HLA-B*39:01:01:04 allele differs from HLA-B*39:01:01 by a C â T substitution in intron 1.
Assuntos
Alelos , Antígeno HLA-B39/genética , Íntrons , Polimorfismo de Nucleotídeo Único , Transplantados , Povo Asiático , Sequência de Bases , Códon/química , Éxons , Expressão Gênica , Genótipo , Antígeno HLA-B39/imunologia , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNA , Imunodeficiência Combinada Severa/patologia , Imunodeficiência Combinada Severa/terapiaRESUMO
HLA-B*39:97N differs from HLA-B*39:01:01 by a two nucleotide insertion at position 604-605.
Assuntos
Alelos , Códon sem Sentido , Éxons , Mutação da Fase de Leitura , Antígeno HLA-B39/genética , Doadores de Tecidos , Sequência de Bases , Transplante de Medula Óssea , Expressão Gênica , Genoma Humano , Antígeno HLA-B39/imunologia , Teste de Histocompatibilidade , Humanos , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
HLA-B*39:01:23 differs from HLA-B*39:01:01 by a single nucleotide substitution at position 153 C > T.
Assuntos
Alelos , Éxons , Antígeno HLA-B39/genética , Polimorfismo de Nucleotídeo Único , Doadores de Tecidos , Sequência de Bases , Transplante de Medula Óssea , Códon/química , Expressão Gênica , Genoma Humano , Antígeno HLA-B39/imunologia , Teste de Histocompatibilidade , Humanos , Íntrons , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
B*38:01 and B*39:06 are present with phenotypic frequencies <2% in the general population, but are of interest as B*39:06 is the B allele most associated with type 1 diabetes susceptibility and 38:01 is most protective. A previous study derived putative main anchor motifs for both alleles based on peptide elution data. The present study has utilized panels of single amino acid substitution peptide libraries to derive detailed quantitative motifs accounting for both primary and secondary influences on peptide binding. From these analyses, both alleles were confirmed to utilize the canonical position 2/C-terminus main anchor spacing. B*38:01 preferentially bound peptides with the positively charged or polar residues H, R, and Q in position 2 and the large hydrophobic residues I, F, L, W, and M at the C-terminus. B*39:06 had a similar preference for R in position 2, but also well-tolerated M, Q, and K. A more dramatic contrast between the two alleles was noted at the C-terminus, where the specificity of B*39:06 was clearly for small residues, with A as most preferred, followed by G, V, S, T, and I. Detailed position-by-position and residue-by-residue coefficient values were generated from the panels to provide detailed quantitative B*38:01 and B*39:06 motifs. It is hoped that these detailed motifs will facilitate the identification of T cell epitopes recognized in the context of two class I alleles associated with dramatically different dispositions towards type 1 diabetes, offering potential avenues for the investigation of the role of CD8 T cells in this disease.
Assuntos
Antígeno HLA-B38/genética , Antígeno HLA-B38/metabolismo , Antígeno HLA-B39/genética , Antígeno HLA-B39/metabolismo , Peptídeos/metabolismo , Sequência de Aminoácidos , Antígeno HLA-B38/imunologia , Antígeno HLA-B39/imunologia , Humanos , Peptídeos/química , Peptídeos/imunologia , Ligação ProteicaRESUMO
The new allele B*39:01:15 differs from B*39:01:01 by a point mutation at position 315 (G>T) of exon 2.
