RESUMO
The allele HLA-C*07:02:60 differs from HLA-C*07:02:01:01 by a silent nucleotide substitution in exon 4.
Assuntos
Alelos , Antígenos HLA-C/genética , Polimorfismo de Nucleotídeo Único , Sequência de Bases , Códon , Éxons , Antígenos HLA-C/classificação , Antígenos HLA-C/imunologia , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Isoformas de Proteínas/classificação , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Alinhamento de Sequência , Doadores não RelacionadosRESUMO
The novel DRB1*01:16 allele differs for G to T substitution at position 595 from DRB3*01:01P.
Assuntos
Alelos , Cadeias HLA-DRB3/genética , Transplante de Células-Tronco Hematopoéticas , Mutação Puntual , Substituição de Aminoácidos , Sequência de Bases , Criança , Clonagem Molecular , Códon , Éxons , Família , Genótipo , Cadeias HLA-DRB3/imunologia , Teste de Histocompatibilidade , Humanos , Itália , Masculino , Dados de Sequência Molecular , Alinhamento de Sequência , Análise de Sequência de DNA , TransplantadosRESUMO
The simultaneous typing of five-HLA loci at high resolution and the availability of pedigree data allowed us to characterize extended five-locus phased haplotypes in 124 Nigerian families and to compare the observed frequencies with those expected by an expectation-maximization algorithm for unphased data. Despite the occurrence of some frequent alleles at each locus (e.g. B*53:01, which is assumed to protect against Plasmodium falciparum), as many as 82% of the sampled individuals carry two unique five-locus haplotypes and only three extended haplotypes with frequency above 1% exhibit significant linkage disequilibrium. Although preliminary, these results reveal an extreme level of HLA diversity in the Nigerian population, which reflects both its multi-ethnic composition and the very ancient demographic history of African populations.
Assuntos
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , Desequilíbrio de Ligação , Alelos , Família , Expressão Gênica , Frequência do Gene , Variação Genética , Genética Populacional , Antígenos HLA-A/imunologia , Antígenos HLA-B/imunologia , Antígenos HLA-C/imunologia , Cadeias beta de HLA-DQ/imunologia , Cadeias HLA-DRB1/imunologia , Teste de Histocompatibilidade , Humanos , Nigéria , LinhagemRESUMO
AIM: To date non-invasive (NIV) mechanical ventilation use is not recommended in chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF) and pH < 7.30 outside a 'protected environment'. We assessed NIV efficacy and feasibility in improving arterial blood gases (ABG) and in-hospital outcome in patients with ARF and severe respiratory acidosis (RA) admitted to an experienced rural medical ward. METHODS: This paper is a prospective pilot cohort study conducted in the General Medicine Ward of Budrio's District Hospital. Two hundred and seventy-two patients with ARF were admitted to our Department, 112, meeting predefined inclusion criteria (pH < 7.35, PaCO2 > 45 mmHg). Patients were divided according to the severity of acidosis into: group A (pH < 7.26), group B (7.26 ≤ pH < 7.30) and group C (7.30 ≤ pH < 7.35). ABG were assessed at admission, at 2-6 h, 24 h, 48 h and at discharge. RESULTS: Group A included 55 patients (24 men, mean age: 80.8 ± 8.3 years), group B 31 (12 men, mean age: 80.3 ± 9.4 years) and group C 26 (15 men, mean age: 78.6 ± 9.9 years). ABG improved within the first hours in 92/112 (82%) patients, who were all successfully discharged. Eighteen percent (20/112) of the patients died during the hospital stay, no significant difference emerged in mortality rate (MR) within the groups (23%, 16% and 8%, for groups A, B and C, respectively) and between patients with or without pneumonia: 8/29 (27%) versus 12/83 (14%). On multivariable analysis, only age and Glasgow Coma Scale had an impact on the clinical outcome. CONCLUSION: In a non-'highly protected' environment such as an experienced medical ward of a rural hospital, NIV is effective not only in patients with mild, but also with severe forms of RA. MR did not vary according to the level of initial pH.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Hospitalização/estatística & dados numéricos , Hipercapnia/terapia , Respiração com Pressão Positiva , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Gasometria , Pressão Positiva Contínua nas Vias Aéreas/métodos , Estudos de Viabilidade , Feminino , Mortalidade Hospitalar , Humanos , Hipercapnia/mortalidade , Hipercapnia/fisiopatologia , Itália/epidemiologia , Masculino , Projetos Piloto , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Mixed chimerism (MC), the simultaneous presence of both host- and donor-derived cells in the recipient, is observed in a large proportion of patients after haematopoietic stem cell transplant (HSCT) to treat haemoglobinopathies. Detected early after transplantation, MC often moves towards complete chimerism, although sometimes it may evolve into graft rejection, especially if the proportion of donor cells is very low. However, some patients develop stable MC, defined as persistent when donor- and host-derived cells coexist for periods longer than 2 years after HSCT. Patients with persistent mixed chimerism (PMC) do not require additional red blood cell support and, regardless of the presence in some cases of an extremely low percentage of donor-derived nucleated cells in the bone marrow, their condition is clinically controlled by an incomplete but functional graft, as they express a two- to fivefold enrichment of donor-derived mature erythrocytes in the peripheral blood. These findings have tremendous implications not only in the context of allogeneic HSCT but also in the design of gene therapy trials based on the autologous transplantation of genetically modified CD34+ cells. Recent studies have shown that durable allograft tolerance has been achieved by induction of haematopoietic chimerism in clinical kidney transplantation, showing the involvement of regulatory T cells. Similarly, it has been shown that the regulatory T cells play a pivotal role in promoting and maintaining immune tolerance in patients that develop a status of PMC after HSCT for Thalassemia.
Assuntos
Quimerismo , Rejeição de Enxerto/imunologia , Transplante de Células-Tronco Hematopoéticas , Hemoglobinopatias/imunologia , Tolerância Imunológica/imunologia , Humanos , Fatores de RiscoRESUMO
The information regarding the probability of finding a matched unrelated donor (MUD) within a relatively short time is crucial for the success of hematopoietic stem cell transplantation (HSCT), particularly in patients with malignancies. In this study, we retrospectively analyzed 315 Italian patients who started a search for a MUD, in order to assess the distribution of human leukocyte antigen (HLA) alleles and haplotypes in this population of patients and to evaluate the probability of finding a donor. Comparing two groups of patients based on whether or not a 10/10 HLA-matched donor was available, we found that patients who had a fully-matched MUD possessed at least one frequent haplotype more often than the others (45.6% vs 14.3%; P = 0.000003). In addition, analysis of data pertaining to the HLA class I alleles distribution showed that, in the first group of patients, less common alleles were under-represented (20.2% vs 40.0%; P = 0.006). Therefore, the presence of less frequent alleles represents a negative factor for the search for a potential compatible donor being successful, whereas the presence of one frequent haplotype represents a positive predictive factor. Antigenic differences between patient and donor observed at C and DQB1 loci, were mostly represented by particular B/C or DRB1/DQB1 allelic associations. Thus, having a particular B or DRB1 allele, linked to multiple C or DQB1 alleles, respectively, might be considered to be associated with a lower probability of a successful search. Taken together, these data may help determine in advance the probability of finding a suitable unrelated donor for an Italian patient.
Assuntos
Seleção do Doador , Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Alelos , Frequência do Gene/genética , Loci Gênicos/genética , Haplótipos/genética , Humanos , Itália , Doadores não RelacionadosRESUMO
The killer cell immunoglobulin-like receptor (KIR)-human leukocyte antigen (HLA) interaction represents an example of genetic epistasis, where the concomitant presence of specific genes or alleles encoding receptor-ligand units is necessary for the activity of natural killer (NK) cells. Although KIR and HLA genes segregate independently, they co-evolved under environmental pressures to maintain particular KIR-HLA functional blocks for species survival. We investigated, in 270 Italian healthy individuals, the distribution of KIR and HLA polymorphisms in three climatic areas (from cold north to warm south), to verify their possible geographical stratification. We analyzed the presence of 13 KIR genes and genotyped KIR ligands belonging to HLA class I: HLA-C, HLA-B and HLA-A. We did not observe any genetic stratification for KIR genes and HLA-C ligands in Italy. By contrast, in a north-to-south direction, we found a decreasing trend for the HLA-A3 and HLA-A11 ligands (P = 0.012) and an increasing trend for the HLA-B ligands carrying the Bw4 epitope (P = 0.0003) and the Bw4 Ile80 epitope (P = 0.0005). The HLA-A and HLA-B KIR ligands were in negative linkage disequilibrium (correlation coefficient -0.1211), possibly as a consequence of their similar function in inhibiting NK cells. The distribution of the KIR-HLA functional blocks was different along Italy, as we observed a north-to-south ascending trend for KIR3DL1, when coupled with HLA-B Bw4 ligands (P = 0.0067) and with HLA-B Bw4 Ile80 (P = 0.0027), and a descending trend for KIR3DL2 when coupled with HLA-A3 and HLA-A11 ligands (P = 0.0044). Overall, people from South Italy preferentially use the KIR3DL1-HLA-B Bw4 functional unit, while those from the North Italy equally use both the KIR3DL2-HLA-A3/A11 and the KIR3DL1-HLA-B Bw4 functional units to fight infections. Thus, only KIR3DL receptors, which exert the unique role of microbial sensors through the specific D0 domain, and their cognate HLA-A and HLA-B ligands are selectively pressured in Italy according to geographical north-to-south distribution.
Assuntos
Genética Populacional , Antígenos HLA/genética , Receptores KIR/genética , Adulto , Alelos , Feminino , Frequência do Gene/genética , Geografia , Humanos , Itália , Ligantes , Desequilíbrio de Ligação/genética , MasculinoRESUMO
The new allele, officially named HLA DRB1*14:129, differs from HLA DRB1*14:54 in exon 2.
Assuntos
Alelos , Cadeias HLA-DRB1/genética , Mutação Puntual , Sequência de Bases , Éxons , Cadeias HLA-DRB1/imunologia , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Transplante de Células-Tronco , Doadores de TecidosRESUMO
The novel allele HLA-DQB1*04:09 differs from DQB1*04:02:01 by three nonsynonymous nucleotide substitutions in exon 2.
Assuntos
Alelos , Cadeias beta de HLA-DQ/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Sequência de Bases , Éxons , Teste de Histocompatibilidade , Humanos , Itália , Dados de Sequência Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
The novel allele human leukocyte antigen(HLA)-DQB1*06:04:04 differs from HLA-DQB1*06:04:01 by a silent nucleotide substitution at codon 75 (TTG â CTG).
Assuntos
Alelos , Cadeias beta de HLA-DQ/genética , Sequência de Bases , Éxons/genética , Humanos , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution.
Assuntos
Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Cadeias HLA-DRB1/genética , Ásia , Etnicidade , Europa (Continente) , Frequência do Gene , Variação Genética , Genética Populacional , Genótipo , Haplótipos , Humanos , Oceania , Grupos PopulacionaisRESUMO
The novel allele HLA-C*16:07:02 differs from HLA-C* 16:07:01 by a silent nucleotide substitution at codon 220 (TAC â TAT).
Assuntos
Antígenos HLA-C/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Alelos , Sequência de Bases , Benin/etnologia , Primers do DNA , Éxons , Feminino , Antígenos HLA-C/imunologia , Haplótipos , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Nucleotídeos/genética , Mutação Puntual , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Análise de Sequência de DNA , IrmãosRESUMO
The novel HLA-C allele C*06:58 shows one nucleotide change from C*06:02:01:01 at nt 366 from G to A, resulting in an amino acid change at codon 98 of exon 3 from Met to Ile.
Assuntos
Alelos , Substituição de Aminoácidos , Éxons/genética , Antígenos HLA-C/genética , Família , Feminino , Humanos , Itália , Masculino , Análise de Sequência de DNARESUMO
The new allele differs from HLA-DPB1*23:01 in exon 3.
Assuntos
Cadeias beta de HLA-DP/genética , Polimorfismo de Nucleotídeo Único , Alelos , Sequência de Bases , Cromossomos Humanos Par 6 , Éxons , Cadeias beta de HLA-DP/imunologia , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Alinhamento de Sequência , Análise de Sequência de DNA , Doadores de TecidosRESUMO
The new allele shows one nucleotide change from C*07:02:01:01 at 351 nt from C to A, resulting in an amino acid change at codon 93 of exon 3 from H to Q.
Assuntos
Alelos , Éxons/genética , Antígenos HLA-C/genética , Mutação/genética , Sequência de Aminoácidos , Sondas de DNA de HLA/genética , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Itália , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Doadores de TecidosRESUMO
HLA-A*03:143 has one nucleotide change from A*03:01: 01:01 at nt 406 from G to C, resulting in an amino acid change at codon 112 of exon 3 from Gly to Arg.
Assuntos
Antígeno HLA-A3/genética , Alelos , Substituição de Aminoácidos , Sequência de Bases , DNA/genética , Éxons , Feminino , Técnicas de Genotipagem , Haplótipos , Teste de Histocompatibilidade , Humanos , Itália , Masculino , Dados de Sequência Molecular , Linhagem , Polimorfismo de Nucleotídeo Único , Homologia de Sequência do Ácido NucleicoRESUMO
Polymorphisms in the 3' untranslated region (3'UTR) of HLA-G, an important player in immunological tolerance, could be involved in post-transcriptional expression control, and their association with different clinical immune-related conditions including autoimmunity and transplantation is of mounting interest. Most studies have focused on a 14 base pair (bp) insertion/deletion (ins/del), while additional single-nucleotide polymorphisms (SNPs) in the HLA-G 3'UTR have been described but not extensively investigated for their clinical relevance. Here we have comparatively studied the association between 3'UTR haplotypes of HLA-G, or the 14 bp ins/del, with clinical outcome of HLA-identical sibling hematopoietic stem cell transplantation (HSCT) in 147 Middle Eastern beta-thalassemia patients. Sequence based typing of 3'UTR HLA-G polymorphisms in the patients and in 102 healthy Italian blood donors showed strong linkage disequilibrium between the 14 bp ins/del and five 3'UTR SNPs, which together could be arranged into eight distinct haplotypes based on expectation-maximization studies, with four predominant haplotypes (UTRs1-4). After HSCT, we found a moderate though not significant association between the presence of UTR-2 in double dose and protection from acute graft versus host disease (hazard ratio (HR) 0.45, 95% confidence intervals (CI): 0.14-1.45; P = 0.18), an effect that was also seen when the corresponding 14 bp ins/ins genotype was considered alone (HR 0.42, 95% CI: 0.16-1.06; P = 0.07). No association was found with rejection or survival. Taken together, our data show that there is no apparent added value of considering entire 3'UTR HLA-G haplotypes for risk prediction after allogeneic HSCT for beta-thalassemia.
Assuntos
Regiões 3' não Traduzidas/genética , Doença Enxerto-Hospedeiro/genética , Antígenos HLA-G/genética , Transplante de Células-Tronco Hematopoéticas , Talassemia beta/genética , Regiões 3' não Traduzidas/imunologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genótipo , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/imunologia , Haplótipos/genética , Haplótipos/imunologia , Humanos , Tolerância Imunológica , Itália , Desequilíbrio de Ligação , Masculino , Mutagênese Insercional , Polimorfismo Genético , Deleção de Sequência , Irmãos , Transplante Homólogo , Resultado do Tratamento , Talassemia beta/imunologia , Talassemia beta/terapiaRESUMO
Human leukocyte antigen (HLA) class I sequence-based typing (SBT) for hematopoietic unrelated donor searching in an Italian Caucasian patient showed the presence of a novel HLA-A allele defined as A*31:48. HLA-A*31:48 has one nucleotide change from A*31:01:02 at nt 727 from C to T, resulting in an amino acid change at codon 219 of exon 4 from Arg to Trp.
Assuntos
Alelos , Substituição de Aminoácidos , Antígenos HLA-A/genética , Mutação de Sentido Incorreto , Adulto , Anemia Aplástica/genética , Anemia Aplástica/terapia , Feminino , HumanosRESUMO
The study of human leukocyte antigen (HLA), allele and haplotype frequencies within populations provides an important source of information for anthropological investigation, organ and hematopoietic stem-cell transplantation purposes as well as disease association studies. As of today, there are no data available in the literature on the HLA structure of the Maldivian population. Altogether 106 families were studied. We used the parents of each family (212 unrelated individuals) to analyze the frequencies of HLA class I and class II allele groups and haplotypes.