RESUMEN
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.
Asunto(s)
Alelos , Secuencia de Bases , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígeno HLA-B7/genética , Análisis de Secuencia de ADN , Secuencia de Aminoácidos , Antígenos HLA-A/química , Antígenos HLA-B/química , Antígeno HLA-B7/química , Haplotipos , Humanos , Péptidos/químicaRESUMEN
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.
Asunto(s)
Predisposición Genética a la Enfermedad , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Antígenos HLA-A/genética , Antígenos HLA-A/metabolismo , Cadenas beta de HLA-DQ/genética , Adulto , Anciano , Alelos , Estudios Transversales , Femenino , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad , Receptores KIR/genética , EspañaRESUMEN
A novel HLA-DRB1*13:216 allele was characterized in a Spanish bone marrow donor.
Asunto(s)
Alelos , Sustitución de Aminoácidos , Exones , Cadenas HLA-DRB1/genética , Mutación , Secuencia de Bases , Trasplante de Médula Ósea , Expresión Génica , Cadenas HLA-DRB1/inmunología , Prueba de Histocompatibilidad , Humanos , Análisis de Secuencia de ADN , España , Donantes de TejidosRESUMEN
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.
Asunto(s)
Alelos , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Genes MHC Clase I/inmunología , Antígenos HLA-A/inmunología , Antígenos HLA-B/inmunología , Humanos , España , Población Blanca/genéticaRESUMEN
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.
RESUMEN
Three novel HLA class II alleles, DRB1*08:70, DQA1*01:13 and DQA1*03:01:03, were characterized.
Asunto(s)
Alelos , Antígenos de Histocompatibilidad Clase II/genética , Secuencia de Aminoácidos , Exones , Cadenas alfa de HLA-DQ/química , Cadenas alfa de HLA-DQ/genética , Cadenas HLA-DRB1/química , Cadenas HLA-DRB1/genética , Antígenos de Histocompatibilidad Clase II/química , Humanos , Linfoma no Hodgkin/genética , Análisis de Secuencia de ADNRESUMEN
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).
Asunto(s)
Alelos , Antígenos HLA-A/genética , Polimorfismo de Nucleótido Simple , Donantes de Tejidos , Secuencia de Bases , Trasplante de Médula Ósea , Codón , Exones , Expresión Génica , Antígenos HLA-A/inmunología , Prueba de Histocompatibilidad , Humanos , Intrones , Datos de Secuencia Molecular , Alineación de SecuenciaRESUMEN
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).
Asunto(s)
Alelos , Antígenos HLA-B/genética , Hispánicos o Latinos/genética , Población Blanca/genética , Secuencia de Bases , Exones/genética , Humanos , Datos de Secuencia Molecular , Alineación de SecuenciaRESUMEN
HLA-B*49:34 shows one nucleotide difference regarding B*49:01:01 at codon 66 (ATC>GTC, I66>V66).
Asunto(s)
Alelos , Antígenos HLA-B/genética , Mutación Puntual , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Donantes de Sangre , Exones , Genotipo , Antígenos HLA-B/inmunología , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Transfusión de Plaquetas , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADN , España , Población BlancaRESUMEN
Two new HLA-A null alleles were characterized, A*11:210N and A*26:107N.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-A/genética , Adulto , Alelos , Secuencia de Aminoácidos , Secuencia de Bases , Humanos , Datos de Secuencia Molecular , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , España , Donantes de TejidosRESUMEN
HLA-B*44:203 shows one nucleotide difference to B*44:03:01 at codon 171 (TAC>CAC, Y171>H171).
Asunto(s)
Alelos , Sustitución de Aminoácidos , Antígenos HLA-B/genética , Polimorfismo de Nucleótido Simple , Secuencia de Bases , Codón , Exones , Sangre Fetal/química , Sangre Fetal/inmunología , Antígenos HLA-B/clasificación , Antígenos HLA-B/inmunología , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Isoformas de Proteínas/clasificación , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , Alineación de Secuencia , EspañaRESUMEN
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.
Asunto(s)
Alelos , Bases de Datos de Ácidos Nucleicos , Cadenas HLA-DRB1/genética , Secuencia de Bases , Humanos , Datos de Secuencia MolecularRESUMEN
HLA-B*08:108 shows one nucleotide difference regarding B*08:01:01 at codon 109 (CTC>TTC, L109>F109).
Asunto(s)
Alelos , Exones , Antígeno HLA-B8/genética , Polimorfismo de Nucleótido Simple , Secuencia de Bases , Trasplante de Médula Ósea , Codón , Antígeno HLA-B8/inmunología , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de Secuencia de ADN , Donantes de Tejidos , Población BlancaRESUMEN
HLA-A*03:168N differs from HLA-A*03:01:01 by a single nucleotide substitution resulting in a coding change Y27X.
Asunto(s)
Alelos , Antígenos HLA-A/genética , Células Madre Hematopoyéticas/metabolismo , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Donantes de Tejidos , Secuencia de Bases , Exones/genética , Humanos , Masculino , Datos de Secuencia Molecular , Noruega , Alineación de Secuencia , SerotipificaciónRESUMEN
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.
Asunto(s)
Aborto Habitual/genética , Transferencia de Embrión , Fertilización In Vitro , Receptores KIR/genética , Adulto , Tasa de Natalidad , Implantación del Embrión/genética , Femenino , Antígenos HLA-C/metabolismo , Haplotipos , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Alelos , Antígenos HLA-B/genética , Cadenas HLA-DRB1/genética , Análisis de Secuencia de ADN , Secuencia de Aminoácidos , Antígenos HLA-B/química , Cadenas HLA-DRB1/química , Humanos , Datos de Secuencia Molecular , Estructura Terciaria de ProteínaRESUMEN
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.
Asunto(s)
Alelos , Rechazo de Injerto , Cadenas beta de HLA-DP/genética , Trasplante de Riñón , Polimorfismo de Nucleótido Simple , Secuencia de Bases , Codón , Exones , Resultado Fatal , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Perú , Alineación de Secuencia , Análisis de Secuencia de ADN , Donantes de TejidosRESUMEN
HLA-B*51:153 shows two nucleotide differences compared with B*51:08 at codon 163 (CTG>ACG).
Asunto(s)
Alelos , Antígenos HLA-B/genética , Mutación Puntual , Secuencia de Bases , Exones , Antígenos HLA-B/inmunología , Haplotipos , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADN , EspañaRESUMEN
Two novels alleles, HLA-A*01:128 and HLA-C*05:88 are characterized.