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
OBJECTIVES: The objective of this study was to seek correlates of immune protection in HIV infection. We sought to elucidate the association between the presence of human leucocyte antigen (HLA) alleles, as well as killer immunoglobulin receptor (KIR) genotypes, and the susceptibility to HIV infection in a Spanish cohort of HIV-exposed seronegative (HESN) individuals. METHODS: A total of 152 individuals were evaluated: 29 HESN individuals in stable heterosexual relationships with an HIV-infected partner admitting high-risk sexual intercourse for at least 12 months prior to inclusion in the study, 61 HIV-infected patients and 62 healthy controls. HLA class I and II alleles and KIR genotypes were assessed in genomic DNA from all individuals in the study by polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) using bead array technology. RESULTS: HESN individuals showed a higher prevalence of HLA-A3 (62%) and HLA-B44 (83%) supertypes compared with HIV-infected individuals (42% and 66%, respectively). Regarding specific HLA alleles, HESN individuals had a higher prevalence of HLA-A*33:01, DRB1*04 and DQB1*03:02 alleles (14%, 34% and 31%, respectively) and a lower prevalence of the HLA-A*02:01 allele (27%) than HIV-infected patients (3%, 15%, 11% and 52%, respectively; P < 0.05). Interestingly, in a multivariate analysis, only the presence of DQB1*03:02 and the absence of A*02:01 alleles were independently associated with HESN status [odds ratio (OR) 3.4 (95% confidence interval (CI) 1.1-10.5) and 0.4 (95% CI: 0.1-0.9), respectively; P < 0.05]. No KIR genotype was associated with susceptibility to HIV infection. CONCLUSIONS: Our data showed that the presence of the HLA class II allele DQB1*03:02 was a correlate of immune protection against HIV infection, while the presence of the HLA class I allele A*02:01 was associated with being infected with HIV.
Assuntos
Predisposição Genética para Doença , Infecções por HIV/genética , Infecções por HIV/imunologia , Antígenos HLA-A/genética , Antígenos HLA-A/metabolismo , Cadeias beta de HLA-DQ/genética , Adulto , Idoso , Alelos , Estudos Transversais , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Receptores KIR/genética , EspanhaRESUMO
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
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
For the past several decades, we have been able to directly probe the motion of atoms that is associated with chemical transformations and which occurs on the femtosecond (10(-15)-s) timescale. However, studying the inner workings of atoms and molecules on the electronic timescale has become possible only with the recent development of isolated attosecond (10(-18)-s) laser pulses. Such pulses have been used to investigate atomic photoexcitation and photoionization and electron dynamics in solids, and in molecules could help explore the prompt charge redistribution and localization that accompany photoexcitation processes. In recent work, the dissociative ionization of H(2) and D(2) was monitored on femtosecond timescales and controlled using few-cycle near-infrared laser pulses. Here we report a molecular attosecond pump-probe experiment based on that work: H(2) and D(2) are dissociatively ionized by a sequence comprising an isolated attosecond ultraviolet pulse and an intense few-cycle infrared pulse, and a localization of the electronic charge distribution within the molecule is measured that depends-with attosecond time resolution-on the delay between the pump and probe pulses. The localization occurs by means of two mechanisms, where the infrared laser influences the photoionization or the dissociation of the molecular ion. In the first case, charge localization arises from quantum mechanical interference involving autoionizing states and the laser-altered wavefunction of the departing electron. In the second case, charge localization arises owing to laser-driven population transfer between different electronic states of the molecular ion. These results establish attosecond pump-probe strategies as a powerful tool for investigating the complex molecular dynamics that result from the coupling between electronic and nuclear motions beyond the usual Born-Oppenheimer approximation.
RESUMO
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
HLA-A*31:01:02:02 differs from A*31:01:02 in a single nucleotide mutation at intron 3, nucleotide position 1000 (G > A).
Assuntos
Alelos , Antígenos HLA-A/genética , Polimorfismo de Nucleotídeo Único , Doadores de Tecidos , Sequência de Bases , Transplante de Medula Óssea , Códon , Éxons , Expressão Gênica , Antígenos HLA-A/imunologia , Teste de Histocompatibilidade , Humanos , Íntrons , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
HLA-B*18:105 shows two nucleotide differences regarding B*18:22 (97 AGC>AGG, 99 TAC>TAT) and B*18:52 (94 ACC>ATC, 95 CTC>ATC).
Assuntos
Alelos , Antígenos HLA-B/genética , Hispânico ou Latino/genética , População Branca/genética , Sequência de Bases , Éxons/genética , Humanos , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
HLA-B*49:34 shows one nucleotide difference regarding B*49:01:01 at codon 66 (ATC>GTC, I66>V66).
Assuntos
Alelos , Antígenos HLA-B/genética , Mutação Puntual , Sequência de Aminoácidos , Substituição de Aminoácidos , Doadores de Sangue , Éxons , Genótipo , Antígenos HLA-B/imunologia , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Transfusão de Plaquetas , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNA , Espanha , População BrancaRESUMO
HLA-B*44:203 shows one nucleotide difference to B*44:03:01 at codon 171 (TAC>CAC, Y171>H171).
Assuntos
Alelos , Substituição de Aminoácidos , Antígenos HLA-B/genética , Polimorfismo de Nucleotídeo Único , Sequência de Bases , Códon , Éxons , Sangue Fetal/química , Sangue Fetal/imunologia , Antígenos HLA-B/classificação , Antígenos HLA-B/imunologia , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Isoformas de Proteínas/classificação , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Alinhamento de Sequência , EspanhaRESUMO
Two new HLA-A null alleles were characterized, A*11:210N and A*26:107N.
Assuntos
Genes MHC Classe I , Antígenos HLA-A/genética , Adulto , Alelos , Sequência de Aminoácidos , Sequência de Bases , Humanos , Dados de Sequência Molecular , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Espanha , Doadores de TecidosRESUMO
HLA-DRB1*11:153 differs from DRB1*11:131 by one nucleotide at position 286 where C > A, (codon 67 CTC>ATC), resulting in an amino acid substitution, 67L>67I.
Assuntos
Alelos , Bases de Dados de Ácidos Nucleicos , Cadeias HLA-DRB1/genética , Sequência de Bases , Humanos , Dados de Sequência MolecularRESUMO
HLA-B*08:108 shows one nucleotide difference regarding B*08:01:01 at codon 109 (CTC>TTC, L109>F109).
Assuntos
Alelos , Éxons , Antígeno HLA-B8/genética , Polimorfismo de Nucleotídeo Único , Sequência de Bases , Transplante de Medula Óssea , Códon , Antígeno HLA-B8/imunologia , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Alinhamento de Sequência , Análise de Sequência de DNA , Doadores de Tecidos , População BrancaRESUMO
HLA-A*03:168N differs from HLA-A*03:01:01 by a single nucleotide substitution resulting in a coding change Y27X.
Assuntos
Alelos , Antígenos HLA-A/genética , Células-Tronco Hematopoéticas/metabolismo , Teste de Histocompatibilidade , Análise de Sequência de DNA , Doadores de Tecidos , Sequência de Bases , Éxons/genética , Humanos , Masculino , Dados de Sequência Molecular , Noruega , Alinhamento de Sequência , SorotipagemRESUMO
STUDY QUESTION: In patients with recurrent miscarriages (RM) or recurrent implantation failure (RIF), does the maternal killer immunoglobulin-like receptor (KIR) haplotype have an impact on live birth rates per cycle after embryo transfer with the patient's own or donated oocytes? SUMMARY ANSWER: After double embryo transfer (DET) in patients with the maternal KIR AA haplotype, a significantly increased early miscarriage rate was observed when the patient's own oocytes were used, and a significantly decreased live birth rate per cycle after embryo transfer was observed when donated oocytes were used. WHAT IS ALREADY KNOWN: Interactions between fetal HLA-C and maternal KIR influence placentation during human pregnancy. There is an increased risk of RM, pre-eclampsia or fetal growth restriction in mothers with the KIR AA haplotype when the fetus has more HLA-C2 genes than the mother. STUDY DESIGN, SIZE AND DURATION: Between 2010 and 2014, we performed a retrospective study that included 291 women, with RM or RIF, who had a total of 1304 assisted reproductive cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnancy, miscarriage and live birth rates per cycle after single or DET, categorized by the origin of the oocytes and the presence of maternal KIR haplotypes, were studied. KIR haplotype regions were defined by the presence of the following KIR genes: Cen-A/2DL3; Tel-A/3DL1 and 2DS4; Cen-B/2DL2 and 2DS2; as well as Tel-B/2DS1 and 3DS1. MAIN RESULTS AND THE ROLE OF CHANCE: Higher rates of early miscarriage per cycle after DET with the patient's own oocytes in mothers with the KIR AA haplotype (22.8%) followed by those with the KIR AB haplotype (16.7%) compared with mothers with the KIR BB haplotype (11.1%) were observed (P = 0.03). Significantly decreased live birth rates per cycle were observed after DET of donated oocytes in mothers with the KIR AA haplotype (7.5%) compared with those with the KIR AB (26.4%) and KIR BB (21.5%) haplotypes (P = 0.006). No statistically significant differences were observed for pregnancy, miscarriage and live birth rates per cycle among those with maternal KIR AA, AB and BB haplotypes after single embryo transfer (SET) with the patient's own or donated oocytes. The large number of cases studied strengthens the results and provides sufficient power to the statistical analysis. LIMITATIONS, REASONS FOR CAUTION: During the IVF procedure, DET induces the expression of more than one paternal HLA-C and the oocyte-derived maternal HLA-C in the oocyte-donation cycles probably behaves like paternal HLA-C. Because this was a retrospective study, we did not have data about the HLA-C of the parent, donor, chorionic villi, or infant, which is a limitation because we cannot show differences according to paternal or oocyte donor HLA-C1 and HLA-C2. WIDER IMPLICATIONS OF THE FINDINGS: These new insights could have an impact on the selection of SET in patients with RM or RIF, and a KIR AA haplotype. Also, it may help in oocyte and/or sperm donor selection by HLA-C in patients with RM or RIF and a KIR AA haplotype. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. The authors have no conflicts of interest to declare.
Assuntos
Aborto Habitual/genética , Transferência Embrionária , Fertilização in vitro , Receptores KIR/genética , Adulto , Coeficiente de Natalidade , Implantação do Embrião/genética , Feminino , Antígenos HLA-C/metabolismo , Haplótipos , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
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
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
Two novels alleles, HLA-A*01:128 and HLA-C*05:88 are characterized.
Assuntos
Alelos , Antígenos HLA-A/genética , Antígenos HLA-C/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Transplante de Medula Óssea , Códon , Antígenos HLA-A/imunologia , Antígenos HLA-C/imunologia , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Mutação , Alinhamento de Sequência , Análise de Sequência de DNA , Espanha , Doadores de TecidosRESUMO
HLA-B*51:153 shows two nucleotide differences compared with B*51:08 at codon 163 (CTG>ACG).