RESUMO
Three new HLA class I alleles were described in the Spanish population. HLA-A*68:169 and -B*39:129 show one amino acid replacement at the α1-domain, compared to A*68:02 (P47 > L47) and -B*39:06 (S11 > A11), respectively. HLA-B*07:298 presents one nucleotide mutation within exon 1, resulting in a new amino acid position -14, L>Q, which has not been previously described in any HLA protein. Prediction of the B*07:298 signal peptide cleavage did not show significant differences in comparison with that obtained for the rest of HLA-B genes.
Assuntos
Alelos , Sequência de Bases , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígeno HLA-B7/genética , Análise de Sequência de DNA , Sequência de Aminoácidos , Antígenos HLA-A/química , Antígenos HLA-B/química , Antígeno HLA-B7/química , Haplótipos , Humanos , Peptídeos/químicaRESUMO
Three new HLA class I alleles, HLA-A*02:620, HLA-B*27:150 and HLA-B*07:05:01:02, were described in the Spanish Caucasoid population.
Assuntos
Alelos , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Genes MHC Classe I/imunologia , Antígenos HLA-A/imunologia , Antígenos HLA-B/imunologia , Humanos , Espanha , População Branca/genéticaRESUMO
A novel HLA-DRB1*13:216 allele was characterized in a Spanish bone marrow donor.
Assuntos
Alelos , Substituição de Aminoácidos , Éxons , Cadeias HLA-DRB1/genética , Mutação , Sequência de Bases , Transplante de Medula Óssea , Expressão Gênica , Cadeias HLA-DRB1/imunologia , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNA , Espanha , Doadores de TecidosRESUMO
An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods. The goal of the 1st and 2nd Spanish KIR Genotyping Workshops was to provide an external proficiency testing program in KIR genotyping for Spanish immunology and transplant laboratories. These workshops were conducted during the years 2014-2016 and consisted of 17 participating laboratories typing a set of 20 samples. The presence/absence of 16 mandatory KIR loci (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 3DL1, 3DL2, 3DL3, 3DS1, and 3DP1) was evaluated per sample. Methods for KIR genotyping included polymerase chain reaction with the use of sequence-specific primers and sequence-specific oligoprobes. Consensus typing was reached in all samples, and the performance of laboratories in external proficiency testing was satisfactory in all cases. The polymorphism detected in the small sample studied in both workshops is indicative of an ample variety of KIR gene profiles in the Spanish population.
Assuntos
Seleção do Doador/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Receptores KIR/genética , Frequência do Gene , Genótipo , Humanos , Células Matadoras Naturais/imunologia , Reação em Cadeia da Polimerase/métodos , Polimorfismo Genético , Controle de QualidadeRESUMO
In this report we describe a case of somatic mutation in the HLA-B gene in the tumour cells of a patient with acute myelogenous leukaemia (AML). Routine human leukocyte antigen (HLA) typing of patient by serology and molecular methodologies rendered discrepant results regarding the expression of a B*15:01 antigen. Sequencing-based typing of a patient's sample including a very high percentage of blast cells revealed the presence of one nucleotide insertion at exon 3, position 440, codon 123. This insertion resulted in a reading frame shift and a premature stop codon at position 152. The mutation was absent in a sample obtained when the patient was in remission. This case report points out the relevance of the sample source for HLA typing in patients with haematological malignancies.
Assuntos
Alelos , Éxons , Mutação da Fase de Leitura , Antígeno HLA-B15/genética , Leucemia Mieloide Aguda/genética , Sequência de Bases , Códon sem Sentido , Feminino , Expressão Gênica , Genótipo , Antígeno HLA-B15/imunologia , Teste de Histocompatibilidade , Humanos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Pessoa de Meia-Idade , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
Characterization of a novel HLA-B null allele, B*15:375N, with a seven base pair deletion in exon 3.
Assuntos
Alelos , Sequência de Bases , Éxons , Antígenos HLA-B/genética , Deleção de Sequência , HumanosRESUMO
Three novel HLA class II alleles, DRB1*08:70, DQA1*01:13 and DQA1*03:01:03, were characterized.
Assuntos
Alelos , Antígenos de Histocompatibilidade Classe II/genética , Sequência de Aminoácidos , Éxons , Cadeias alfa de HLA-DQ/química , Cadeias alfa de HLA-DQ/genética , Cadeias HLA-DRB1/química , Cadeias HLA-DRB1/genética , Antígenos de Histocompatibilidade Classe II/química , Humanos , Linfoma não Hodgkin/genética , Análise de Sequência de DNARESUMO
The new HLA-DPB1*142:01 allele differs from DPB1*26:01:02 and DPB1*56:01 at codons 65 (I65>L65) and 35 (F35>Y35), respectively.
Assuntos
Alelos , Rejeição de Enxerto , Cadeias beta de HLA-DP/genética , Transplante de Rim , Polimorfismo de Nucleotídeo Único , Sequência de Bases , Códon , Éxons , Evolução Fatal , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Peru , Alinhamento de Sequência , Análise de Sequência de DNA , Doadores de TecidosRESUMO
HLA-B*51:153 shows two nucleotide differences compared with B*51:08 at codon 163 (CTG>ACG).
Assuntos
Alelos , Antígenos HLA-B/genética , Mutação Puntual , Sequência de Bases , Éxons , Antígenos HLA-B/imunologia , Haplótipos , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNA , EspanhaRESUMO
HLA-B*49:24 shows one nucleotide difference regarding B*49:10 at codon 12 (ATG>GTG). DRB1*03:64 differs from DRB1*03:01:01 in one amino acid residue at position 59, E>Q.
Assuntos
Alelos , Antígenos HLA-B/genética , Cadeias HLA-DRB1/genética , Análise de Sequência de DNA , Sequência de Aminoácidos , Antígenos HLA-B/química , Cadeias HLA-DRB1/química , Humanos , Dados de Sequência Molecular , Estrutura Terciária de ProteínaRESUMO
B*08:79 is composed by partial B*08:01:01 and B*07:06 sequences because of a possible recombination event within intron 2.
Assuntos
Alelos , Éxons/genética , Genoma Humano/genética , Antígeno HLA-B7/genética , Antígeno HLA-B8/genética , Recombinação Genética/genética , Sequência de Bases , Humanos , Dados de Sequência MolecularRESUMO
The novel HLA-B*44:130 allele was found in a Spanish donor. B*44:130 differs from B*44:40 by four nucleotide changes at codons 11, 12 and 24, producing three amino acid replacements, 11A>S, 12M>V and 24T>S.
Assuntos
Antígenos HLA-B/genética , Alelos , Sequência de Bases , Códon , Genótipo , Humanos , Dados de Sequência Molecular , População BrancaRESUMO
The new HLA-C allele C*07:170 differs from C*07:01:01 by two nucleotides at exon 3.
Assuntos
Antígenos HLA-C/genética , Polimorfismo de Nucleotídeo Único , Alelos , Sequência de Aminoácidos/genética , Substituição de Aminoácidos , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
Human leukocyte antigen (HLA) class I sequence-based typing (SBT) for hematopoietic unrelated donor searching in a Romanian Caucasian patient showed the presence of a novel HLA-B allele defined as B*0777. HLA-B*0777 has two nucleotides changes at the same codon from B*0707, resulting an amino acid replacement 99Y > 99S.
Assuntos
Alelos , Antígenos HLA-B/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação , Humanos , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
The association between human leukocyte antigen (HLA) class II antigens and celiac disease (CD) was analyzed in a Spanish population. No association with DRB1*04 and DQB1*0302 was noted. The main associated haplotype (70.8%) was DRB1*03-DQB1*0201-DQA1*0501(DR3-DQ2), followed by DRB1*07-DQB1*0202-DQA1*0201 (DR7-DQ2) haplotype, which is associated with DRB1*11-DQB1*0301-DQA1*0505 (DR11-DQ7). The combinations of DR3-DQ2 with DR7-DQ2, and DR7-DQ2 with DR11-DQ7, present a twofold risk compared with each haplotype in homozygosis. An independence test in DR3-DQ2 haplotype found that association with CD was attributable to the whole haplotype, but for DR7-DQ2 was secondary to DQB1/DQA1. There is no need of a double gene dosage to increase the risk. CD-associated alleles typing demonstrates a very high negative predictive value to exclude CD in risk groups.
Assuntos
Alelos , Antígenos HLA-D/genética , Haplótipos/genética , Doença Celíaca/genética , Predisposição Genética para Doença , Genótipo , Humanos , Grupos Populacionais , EspanhaRESUMO
The objective of this study was to analyze the proliferative response of BALB/cmice lymphocytes after in vitro irradiation (0.05 to 6 Gy). The capability of irradiatedlymphocytes for proliferating without any stimulation and after activation withspecific T and B cell mitogens has been evaluated. The results show that ionizingradiation significantly inhibits spontaneous cellular proliferation and that induced bymitogens and that variations in the degree of inhibition are found depending on theinducing proliferation mitogens and the dosage applied. The conclusion drawn is thatdifferent lymphocyte populations have different radiosensitivities, being B cells moresensitive to ionizing irradiation than T cells. Besides, the effects of gamma-irradiationvary according to the different subpopulations of T cells or, alternatively, to differentT-dependent activation mechanisms (AU)
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Assuntos
Animais , Masculino , Camundongos , Feminino , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/citologia , Proliferação de Células , Subpopulações de Linfócitos T/imunologia , Concanavalina A/administração & dosagem , Relação Dose-Resposta Imunológica , Lipopolissacarídeos/administração & dosagem , Mitógenos/imunologia , Fito-Hemaglutininas/administração & dosagem , Tolerância a Radiação , Subpopulações de Linfócitos B , Raios gama , Relação Dose-Resposta à Radiação , Mitógenos/administração & dosagem , Proliferação de Células/efeitos da radiação , Subpopulações de Linfócitos B/efeitos da radiação , Subpopulações de Linfócitos T , Subpopulações de Linfócitos T/efeitos da radiação , Células Cultivadas , Ativação LinfocitáriaRESUMO
The objective of this study was to analyze the proliferative response of BALB/c mice lymphocytes after in vitro irradiation (0.05 to 6 Gy). The capability of irradiated lymphocytes for proliferating without any stimulation and after activation with specific T and B cell mitogens has been evaluated. The results show that ionizing radiation significantly inhibits spontaneous cellular proliferation and that induced by mitogens and that variations in the degree of inhibition are found depending on the inducing proliferation mitogens and the dosage applied. The conclusion drawn is that different lymphocyte populations have different radiosensitivities, being B cells more sensitive to ionizing irradiation than T cells. Besides, the effects of gamma-irradiation vary according to the different subpopulations of T cells or, alternatively, to different T-dependent activation mechanisms.
Assuntos
Subpopulações de Linfócitos B/imunologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Raios gama , Mitógenos/administração & dosagem , Subpopulações de Linfócitos T/imunologia , Animais , Subpopulações de Linfócitos B/citologia , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/efeitos da radiação , Células Cultivadas , Concanavalina A/administração & dosagem , Relação Dose-Resposta Imunológica , Relação Dose-Resposta à Radiação , Feminino , Lipopolissacarídeos/administração & dosagem , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitógenos/imunologia , Fito-Hemaglutininas/administração & dosagem , Mitógenos de Phytolacca americana/administração & dosagem , Tolerância a Radiação/imunologia , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos da radiaçãoRESUMO
Genetic predisposition to celiac disease (CD) is determined primarily by the human leukocyte antigen (HLA) genes (CELIAC1 region; 6p21), although many loci are involved in disease susceptibility. First, we have analysed a large series of CD patients from the Spanish Mediterranean region who had previously been characterised for the HLA complex. We have investigated how relevant regions contribute to CD susceptibility: CELIAC3 (CD28/CTLA4/ICOS region on 2q33) and CELIAC4 (19p13) as well as the tumour necrosis factor alpha (TNF-alpha) and the linfotoxin loci by case-control and association analyses. We highlight the association with the +49*A allele of cytotoxic T-lymphocyte-associated antigen 4 locus (P = 0.01), and the -308*A of TNF-alpha locus (P = 0.0008) in DQ2 individuals, although an independent role for TNF-alpha as risk factor has not been proven. Moreover, we do not confirm the association with the CELIAC4 region polymorphisms described in other populations.
Assuntos
Antígenos CD/genética , Antígenos de Diferenciação/genética , Doença Celíaca/genética , Predisposição Genética para Doença , Miosinas/genética , Alelos , Antígeno CTLA-4 , Estudos de Casos e Controles , Doença Celíaca/metabolismo , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Polimorfismo Genético , Espanha , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: The association of melanoma with HLA class II loci is under extensive debate. Different investigators have found discrepant results due to, at least in part, sample size, patient series heterogeneity, choice of control population and differences in the techniques employed for the detection of HLA antigens and alleles. OBJECTIVES: This study was designed to analyse the possible association of melanoma with HLA class II loci with regard to different clinic pathological factors and to investigate other risk factors for melanoma susceptibility, such as HLA homozygosity. PATIENTS AND METHODS: HLA-DRB1, -DQA1 and -DQB1 genotyping was performed for 117 eastern Spanish patients presenting with primary melanoma. RESULTS: Although there were no significant alterations in the phenotypic frequencies of HLA-DQA1, -DQB1 or -DRB1 alleles in any subgroup of patients when compared with controls, patients exhibited a statistically significant increase in HLA-DQA1 homozygosity rate. This DQA1 homozygosity-specific association was particularly dependent on some features in melanoma patients such as light hair colour, skin type I or II, early age at diagnosis, absence of atypical naevi, or abscence of atypical naevus syndrome phenotype (aetiological fractions about 10-20%). Analysis of homozygosity for single DQA1 alleles showed an increased homozygosity rate for DQA1*0505 and DQA1*0301 in comparison with controls. These DQA1 alleles are in strong linkage disequilibrium with DQB1*0301 in white populations, and DQB1*0301 homozygous individuals were significantly increased in red in or fair-haired patients (relative risk 5.65). CONCLUSIONS: Our results indicate that the contribution of HLA class II alleles to primary melanoma incidence is not significant in the Spanish population. However, homozygosity for the HLA-DQA1 locus (and, perhaps, for the HLA-DQB1*0301 allele) might be considered a potential risk factor for developing melanoma depending on the person's genetic background and, perhaps, on certain environmental conditions.
