RESUMO
A single nucleotide substitution in the exon 3 gives rise to the novel HLA-DQA1*05:73 allele.
Assuntos
Alelos , Substituição de Aminoácidos , Éxons , Cadeias alfa de HLA-DQ , Teste de Histocompatibilidade , Humanos , Cadeias alfa de HLA-DQ/genética , Éxons/genética , Teste de Histocompatibilidade/métodos , Análise de Sequência de DNA/métodos , Polimorfismo de Nucleotídeo Único , Sequência de Bases , CódonRESUMO
[This corrects the article DOI: 10.3389/fimmu.2024.1443096.].
Assuntos
Biomarcadores , Influenza Humana , Interleucina-15 , Interleucina-8 , Humanos , Influenza Humana/imunologia , Influenza Humana/complicações , Prognóstico , Interleucina-8/sangueRESUMO
Introduction: Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression. Methods: We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission. Results: Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71). Discussion: Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.
Assuntos
Biomarcadores , Influenza Humana , Interleucina-15 , Interleucina-8 , Humanos , Influenza Humana/imunologia , Influenza Humana/sangue , Masculino , Feminino , Biomarcadores/sangue , Prognóstico , Pessoa de Meia-Idade , Interleucina-15/sangue , Idoso , Estudos Prospectivos , Interleucina-8/sangue , AdultoRESUMO
Two different single nucleotide substitutions in intron 2 give rise to novel HLA-DQB1*03:02:01 alleles.
Assuntos
Alelos , Cadeias beta de HLA-DQ , Íntrons , Humanos , Teste de Histocompatibilidade , Cadeias beta de HLA-DQ/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Two nucleotide substitutions in intronic regions give rise to the novel alleles: HLA-B*35:01:01:39 and -B*35:03:01:32.
Assuntos
Genes MHC Classe I , Antígenos HLA-B , Humanos , Alelos , Antígenos HLA-B/genética , Íntrons , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Three nucleotide substitutions in intronic regions give rise to the novel alleles: HLA-DQB1*03:01:01:54, -DQB1*03:01:01:56, -DQB1*03:01:01:58.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Cadeias beta de HLA-DQ/genética , ÍntronsRESUMO
HLA-DPA1*02:01:25 differs from DPA1*02:01:01:02 by a synonymous transition in exon 2.
Assuntos
Cadeias alfa de HLA-DP , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Cadeias alfa de HLA-DP/genética , Éxons/genéticaRESUMO
Seven different single nucleotide substitutions in non-coding regions gave rise to novel HLA-DPA1*01:03:01 variants.
Assuntos
Cadeias alfa de HLA-DP , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Cadeias alfa de HLA-DP/genética , Teste de HistocompatibilidadeRESUMO
Characterization by next-generation sequencing of four novel HLA alleles: C*17:03:01:07, C*16:01:01:39, B*15:17:01:07, and B*44:03:01:57.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Nucleotídeos , Humanos , Regiões 3' não Traduzidas , AlelosRESUMO
HLA-DQA1*05:71, the first HLA-DQA1 allele with Aspartic Acid at residue 208 in the transmembrane domain.
Assuntos
Ácido Aspártico , Humanos , Ácido Aspártico/genética , Alelos , Análise de Sequência de DNA , Cadeias alfa de HLA-DQ/genéticaRESUMO
The novel HLA-DQB1*03:02:01:14 was likely generated by a recombination event between DQB1*03:02:01:01 and DQB1*03:03:02:01.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Recombinação Genética , Humanos , Alelos , Cadeias beta de HLA-DQ/genéticaRESUMO
Two transitions in intronic regions give rise to the novel alleles: HLA-DQB1*05:02:01:13 and HLA-DQB1*05:02:01:14.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Cadeias beta de HLA-DQ/genética , ÍntronsRESUMO
A missense nucleotide substitution in codon -17 in the leader peptide results in the novel HLA-DRB1*04:354 allele.
Assuntos
Nucleotídeos , Valina , Humanos , Cadeias HLA-DRB1/genética , Alelos , Valina/genética , Éxons/genéticaRESUMO
The failure to identify HLA null alleles in bone marrow transplantation could be life-threatening because this could result in an HLA mismatch with the ability to trigger the graft-vs-host disease (GVHD) and to reduce patient's survival. In this report we describe the identification and characterization of the novel HLA-DPA1*02:66:02N allele with a non-sense codon in exon 2. This new allele was discovered in two unrelated bone marrow donors during routine HLA-typing using next-generation sequencing (NGS). DPA1*02:66:02N is homologous to DPA1*02:01:01:03 with a single nucleotide difference in exon 2, codon 50, where the replacement of C located at genomic position 3825 by T, causes the formation of a premature stop codon (TGA), resulting in a null allele. This description illustrates the benefits of HLA typing by NGS since it permits to reduce ambiguities, identify new alleles, analyze multiple HLA loci and improve transplantation outcome.
Assuntos
Códon sem Sentido , Cadeias alfa de HLA-DP , Humanos , Alelos , Cadeias alfa de HLA-DP/genética , Éxons/genética , Códon , Teste de Histocompatibilidade/métodosRESUMO
Patients on hemodialysis show dysregulated immunity, basal hyperinflammation and a marked vulnerability to COVID-19. We evaluated the immune profile in COVID-19 hemodialysis patients and the changes associated with clinical deterioration after the hemodialysis session. Recruited patients included eight hemodialysis subjects with active, PCR-confirmed SARS-CoV-2 infection, five uninfected hemodialysis patients and five healthy controls. In SARS-CoV-2-infected hemodialysis patients TNF-α, IL-6 and IL-8 were particularly increased. Lymphopenia was mostly due to reduction in CD4+ T, B and central memory CD8+ T cells. There was a predominance of classical and intermediate monocytes with reduced HLA-DR expression and enhanced production of pro-inflammatory molecules. Immune parameters were analysed pre- and post-hemodialysis in three patients with COVID-19 symptoms worsening after the hemodialysis session. There was a higher than 2.5-fold increase in GM-CSF, IFN-γ, IL-1ß, IL-2, IL-6, IL-17A and IL-21 in serum, and augmentation of monocytes-derived TNF-α, IL-1ß and IL-8 and CXCL10 (p < 0.05). In conclusion, COVID-19 in hemodialysis patients associates with alteration of lymphocyte subsets, increasing of pro-inflammatory cytokines and monocyte activation. The observed worsening during the hemodialysis session in some patients was accompanied by augmentation of particular inflammatory cytokines, which might suggest biomarkers and therapeutic targets to prevent or mitigate the hemodialysis-related deterioration during SARS-CoV-2 infection.
Assuntos
COVID-19 , Falência Renal Crônica , Humanos , SARS-CoV-2/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6 , Interleucina-8 , Citocinas/metabolismo , Falência Renal Crônica/terapia , Diálise RenalRESUMO
A synonymous substitution in exon 2 and intronic insertion results in the novel HLA-DQA1*01:04:07 allele.
Assuntos
Antígenos HLA-DQ , Humanos , Antígenos HLA-DQ/genética , Alelos , Cadeias alfa de HLA-DQ/genética , ÉxonsRESUMO
A nonsynonymous nucleotide substitution in exon 1 results in the novel HLA-DQB1*03:493 allele.
Assuntos
Ácido Glutâmico , Sinais Direcionadores de Proteínas , Humanos , Alelos , Ácido Glutâmico/genética , Sequência de Bases , Cadeias beta de HLA-DQ/genéticaRESUMO
NK degranulation plays an important role in the cytotoxic activity of innate immunity in the clearance of intracellular infections and is an important factor in the outcome of the disease. This work has studied NK degranulation and innate immunological profiles and functionalities in COVID-19 patients and its association with the severity of the disease. A prospective observational study with 99 COVID-19 patients was conducted. Patients were grouped according to hospital requirements and severity. Innate immune cell subpopulations and functionalities were analyzed. The profile and functionality of innate immune cells differ between healthy controls and severe patients; CD56dim NK cells increased and MAIT cells and NK degranulation rates decreased in the COVID-19 subjects. Higher degranulation rates were observed in the non-severe patients and in the healthy controls compared to the severe patients. Benign forms of the disease had a higher granzymeA/granzymeB ratio than complex forms. In a multivariate analysis, the degranulation capacity resulted in a protective factor against severe forms of the disease (OR: 0.86), whereas the permanent expression of NKG2D in NKT cells was an independent risk factor (OR: 3.81; AUC: 0.84). In conclusion, a prompt and efficient degranulation functionality in the early stages of infection could be used as a tool to identify patients who will have a better evolution.