RESUMO
HLA-C*07:04:29 differs from HLA-C*07:04:01:01 by a single substitution in exon 4.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Alelos , China , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos HLA-C/genética , População do Leste AsiáticoRESUMO
A novel HLA-C*07 allele, now officially designated HLA-C*07:02:150, was identified by next-generation sequencing.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
The novel allele HLA-C*07:02:147 differs from HLA-C*07:02:01:01 by one synonymous nucleotide substitution in exon 2.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Éxons/genética , NucleotídeosRESUMO
HLA-C*03:94:02 differs from HLA-C*03:94:01 by a single nucleotide substitution in exon 2 (codon 17 GGA->GGG).
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Sequenciamento de Nucleotídeos em Larga Escala , ChinaRESUMO
Novel HLA-B*55:01:31, HLA-C*07:1113 alleles and confirmatory HLA-C*12:392 allele were detected during the HLA typing process.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Alelos , Antígenos HLA-C/genética , Antígenos HLA-B/genética , Teste de HistocompatibilidadeRESUMO
One nucleotide substitution in codon 264 of HLA-C*07:02:01:01 results in a novel allele, HLA-C*07:359.
Assuntos
Antígenos HLA-C , Polimorfismo de Nucleotídeo Único , Humanos , Sequência de Bases , Antígenos HLA-C/genética , Alelos , Substituição de Aminoácidos , Éxons/genética , Análise de Sequência de DNA/métodos , Teste de Histocompatibilidade , Doadores de Tecidos , TaiwanRESUMO
HLA-C*06:376N differs from HLA-C*06:02:01:01 by seven nucleotide changes in exon 2, intron 2, and exon 3.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Análise de Sequência de DNA , China , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Behçet's disease (BD) manifests as an autoimmune disorder featuring recurrent ulcers and multi-organ involvement, influenced by genetic factors associated with both HLA and non-HLA genes, including TNF-α and ERAP1. The study investigated the susceptible alleles of both Class I and II molecules of the HLA gene in 56 Thai BD patients and 192 healthy controls through next-generation sequencing using a PacBio kit. The study assessed 56 BD patients, primarily females (58.9%), revealing diverse manifestations including ocular (41.1%), vascular (35.7%), skin (55.4%), CNS (5.4%), and GI system (10.7%) involvement. This study found associations between BD and HLA-A*26:01:01 (OR 3.285, 95% CI 1.135-9.504, P-value 0.028), HLA-B*39:01:01 (OR 6.176, 95% CI 1.428-26.712, P-value 0.015), HLA-B*51:01:01 (OR 3.033, 95% CI 1.135-8.103, P-value 0.027), HLA-B*51:01:02 (OR 6.176, 95% CI 1.428-26.712, P-value 0.015), HLA-C*14:02:01 (OR 3.485, 95% CI 1.339-9.065, P-value 0.01), HLA-DRB1*14:54:01 (OR 1.924, 95% CI 1.051-3.522, P-value 0.034), and HLA-DQB1*05:03:01 (OR 3.00, 95% CI 1.323-6.798, P-value 0.008). However, after Bonferroni correction none of these alleles were found to be associated with BD. In haplotype analysis, we found a strong linkage disequilibrium in HLA-B*51:01:01, HLA-C*14:02:01 (P-value 0.0, Pc-value 0.02). Regarding the phenotype, a significant association was found between HLA-DRB1*14:54:01 (OR 11.67, 95% CI 2.86-47.57, P-value 0.001) and BD with ocular involvement, apart from this, no distinct phenotype-HLA association was documented. In summary, our study identifies specific HLA associations in BD. Although limited by a small sample size, we acknowledge the need for further investigation into HLA relationships with CNS, GI, and neurological phenotypes in the Thai population.
Assuntos
Síndrome de Behçet , Feminino , Humanos , Síndrome de Behçet/epidemiologia , Cadeias HLA-DRB1/genética , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos HLA-C/genética , Tailândia , Antígenos HLA-B/genética , Alelos , Tecnologia , Predisposição Genética para Doença , Aminopeptidases/genética , Antígenos de Histocompatibilidade MenorRESUMO
Introduction: Psoriasis is a T-cell mediated autoimmune skin disease. HLA-C*06:02 is the main psoriasis-specific risk gene. Using a Vα3S1/Vß13S1 T-cell receptor (TCR) from a lesional psoriatic CD8+ T-cell clone we had discovered that, as an underlying pathomechanism, HLA-C*06:02 mediates an autoimmune response against melanocytes in psoriasis, and we had identified an epitope from ADAMTS-like protein 5 (ADAMTSL5) as a melanocyte autoantigen. The conditions activating the psoriatic autoimmune response in genetically predisposed individuals throughout life remain incompletely understood. Here, we aimed to identify environmental antigens that might trigger autoimmunity in psoriasis because of TCR polyspecificity. Methods: We screened databases with the peptide recognition motif of the Vα3S1/Vß13S1 TCR for environmental proteins containing peptides activating this TCR. We investigated the immunogenicity of these peptides for psoriasis patients and healthy controls by lymphocyte stimulation experiments and peptide-loaded HLA-C*06:02 tetramers. Results: We identified peptides from wheat, Saccharomyces cerevisiae, microbiota, tobacco, and pathogens that activated both the Vα3S1/Vß13S1 TCR and CD8+ T cells from psoriasis patients. Using fluorescent HLA-C*06:02 tetramers loaded with ADAMTSL5 or wheat peptides, we find that the same CD8+ T cells may recognize both autoantigen and environmental antigens. A wheat-free diet could alleviate psoriasis in several patients. Discussion: Our results show that due to TCR polyspecificity, several environmental antigens corresponding to previously suspected psoriasis risk conditions converge in the reactivity of a pathogenic psoriatic TCR and might thus be able to stimulate the psoriatic autoimmune response against melanocytes. Avoiding the corresponding environmental risk factors could contribute to the management of psoriasis.
Assuntos
Autoimunidade , Psoríase , Humanos , Linfócitos T CD8-Positivos , Antígenos HLA-C , Autoantígenos , Peptídeos , Receptores de Antígenos de Linfócitos T , Proteínas ADAMTSRESUMO
Helicobacter pylori (H. pylori) seems to play causative roles in gastric cancers. H. pylori has also been detected in established gastric cancers. How the presence of H. pylori modulates immune response to the cancer is unclear. The cytotoxicity of natural killer (NK) cells, toward infected or malignant cells, is controlled by the repertoire of activating and inhibitory receptors expressed on their surface. Here, we studied H. pylori-induced changes in the expression of ligands, of activating and inhibitory receptors of NK cells, in the gastric adenocarcinoma AGS cells, and their impacts on NK cell responses. AGS cells lacked or had low surface expression of the class I major histocompatibility complex (MHC-I) molecules HLA-E and HLA-C-ligands of the major NK cell inhibitory receptors NKG2A and killer-cell Ig-like receptor (KIR), respectively. However, AGS cells had high surface expression of ligands of activating receptors DNAM-1 and CD2, and of the adhesion molecules LFA-1. Consistently, AGS cells were sensitive to killing by NK cells despite the expression of inhibitory KIR on NK cells. Furthermore, H. pylori enhanced HLA-C surface expression on AGS cells. H. pylori infection enhanced HLA-C protein synthesis, which could explain H. pylori-induced HLA-C surface expression. H. pylori infection enhanced HLA-C surface expression also in the hepatoma Huh7 and HepG2 cells. Furthermore, H. pylori-induced HLA-C surface expression on AGS cells promoted inhibition of NK cells by KIR, and thereby protected AGS cells from NK cell cytotoxicity. These results suggest that H. pylori enhances HLA-C expression in host cells and protects them from the cytotoxic attack of NK cells expressing HLA-C-specific inhibitory receptors.
Assuntos
Adenocarcinoma , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Adenocarcinoma/genética , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Helicobacter pylori/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos HLA-C/genética , Antígenos HLA-C/metabolismo , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Receptores Imunológicos/metabolismo , Receptores KIR/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologiaRESUMO
HLA-C*06:372 differs from HLA-C*06:02:01:01 by a single substitution in exon 4.
Assuntos
Etnicidade , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Genes MHC Classe I , Células-TroncoRESUMO
HLA-C*08:273 differs from HLA-C*08:01:01:01 by one nucleotide in exon 2.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Nucleotídeos , China , Análise de Sequência de DNARESUMO
The novel HLA-C*14:159 allele was detected during the routine HLA typing for kidney transplantation.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Sequenciamento de Nucleotídeos em Larga Escala , Teste de HistocompatibilidadeRESUMO
HLA-C*17:01:01:29 differs from the HLA-C*17:01:01:05 allele by one nucleotide substitution in the 3'UTR.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Grécia , Alelos , Regiões 3' não TraduzidasRESUMO
HLA-C*04:01:01:174 differs from the HLA-C*04:01:01:06 allele by one nucleotide substitution in the intron 5.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Grécia , Alelos , ÍntronsRESUMO
HLA-C*01:02:01:70 differs from the HLA-C*01:02:01:01 allele by one nucleotide substitution in the intron 4.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Grécia , Alelos , ÍntronsRESUMO
BACKGROUND AND OBJECTIVES: The implications of the genetic component in the initiation and development of chronic lymphoproliferative disorders have been the subject of intense research efforts. Some of the most important genes involved in the occurrence and evolution of these pathologies are the HLA genes. The aim of this study is to analyze, for the first time, possible associations between chronic lymphoproliferative diseases and certain HLA alleles in the Romanian population. MATERIALS AND METHODS: This study included 38 patients with chronic lymphoproliferative disorders, diagnosed between 2021 and 2022 at Fundeni Clinical Institute, Bucharest, Romania, and 50 healthy controls. HLA class I and class II genes (HLA-A/B/C, HLA-DQB1/DPB1/DRB1) were investigated by doing high resolution genotyping using sequence specific primers (SSP). RESULTS: Several HLA alleles were strongly associated with chronic lymphoproliferative disorders. The most important finding was that the HLA-C*02:02 (p = 0.002, OR = 1.101), and HLA-C*12:02 (p = 0.002, OR = 1.101) have a predisposing role in the development of chronic lymphoproliferative disorders. Moreover, we identified that HLA-A*11:01 (p = 0.01, OR = 0.16), HLA-B*35:02 (p = 0.037, OR = 0.94), HLA-B*81:01 (p = 0.037, OR = 0.94), HLA-C*07:02 (p = 0.036, OR = 0.34), HLA-DRB1*11:01 (p = 0.021, OR = 0.19), and HLA-DRB1*13:02 (p = 0.037, OR = 0.94), alleles have protective roles. CONCLUSIONS: Our study indicates that HLA-C*02:02 and HLA-C*12:02 are positively associated with chronic lymphoproliferative disorders for our Romanian patients while HLA-DRB1*11:01, HLA-DRB1*13:02, and HLA-B*35:02 alleles have a protective role against these diseases.
Assuntos
Transtornos Linfoproliferativos , Neoplasias , Humanos , Romênia , Estudos de Casos e Controles , Antígenos HLA-C , Cadeias HLA-DRB1 , Imunogenética , Antígenos HLA-B , Antígenos HLA-ARESUMO
Objective: To establish prediction models for human leukocyte antigen (HLA) haplotypes and HLA genotypes, and verify the prediction accuracy. Methods: The prediction models were established based on the characteristic of HLA haplotype inheritance and linkage disequilibrium (LD), as well as the invention patents and software copyrights obtained. The models include algorithm and reference databases such as HLA A-C-B-DRB1-DQB1 high-resolution haplotypes database, B-C and DRB1-DQB1 LD database, G group alleles table, and NMDP Code alleles table. The prediction algorithm involves data processing, comparison with reference data, filtering results, probability calculation and ranking, confidence degree estimation, and output of prediction results. The accuracy of the predictions was verified by comparing them with the correct results, and the relationship between prediction accuracy and the probability distribution and confidence degree of the predicted results was analyzed. Results: The HLA haplotypes and genotypes prediction models were established. The prediction algorithm included the prediction of A-C-B-DRB1-DQB1 haplotypes according to HLA-A, B, DRB1, C, DQB1 genotypes, the prediction of C and DQB1 high-resolution results according to A, B and DRB1 high-resolution results, and the prediction of A, B, DRB1, C and DQB1 high resolution results according to the A, B and DRB1 intermediate or low resolution results. Validation results of "Predicting A-C-B-DRB1-DQB1 haplotypes basing on HLA-A, B, DRB1, C, DQB1 genotypes" model: for 787 data, the accuracy was 94.0% (740/787) with 740 correct predictions, 34 incorrect predictions, and 13 instances with no predicted results. For 847 data, the accuracy was 100% (847/847). The 2 411 and 2 594 haplotype combinations predicted from 787 and 847 data were grouped according to confidence degree, the accuracy was 100% (48/48, 114/114) for a confidence degree of 1, 96.2% (303/315) and 97.8% (409/418) for a confidence degree of 2 respectively. Validation results of "Predicting A, B, DRB1 and C, DQB1 high-resolution genotypes basing on HLA-A, B, DRB1 high, intermediate, or low resolution genotypes" model: when predicting C and DQB1 high resolution genotypes basing on A, B, and DRB1 high resolution genotypes, 89.3% (1 459/1 634) of the predictions were correct. The accuracy for the top 2 predicted probability (GPP) ranking was 79.2% (1 156/1 459), and for the top 10, it was 95.0% (1 386/1 459). Furthermore, when GPP≥90% and GPP 50%-90%, the prediction accuracy was 81.3% (209/257) and 72.8% (447/614) respectively. The accuracy of predicting C and DQB1 high resolution genotypes basing on the results of A, B, and DRB1 high resolution genotypes from the China Marrow Donor Program was 87.0% (20/23). The accuracy of predicting A, B, DRB1, C, and DQB1 high resolution genotypes basing on the results of A, B, and DRB1 intermediate or low-resolution genotypes was 70.0% (7/10) and 52.5% (21/40) respectively. When predicting whether the patient is likely to have a HLA 10/10 matched donor, the accuracy of the top 2 GPP combinations with a proportion of ≥50% was 85.7% (6/7). Conclusions: When using A, B, DRB1, C, DQB1 genotypes to predict A-C-B-DRB1-DQB1 haplotype combinations, the results with a confidence degree of 1 and 2 are reliable. When predicting C and DQB1 genotypes according to A, B and DRB1 genotypes, the top 10 results ranked by GPP are reliable, and the top 2 results with GPP≥50% are more reliable.
Assuntos
Antígenos HLA-B , Antígenos HLA-C , Humanos , Haplótipos , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Frequência do Gene , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Antígenos de Histocompatibilidade Classe I/genética , Genótipo , Antígenos HLA-A/genética , AlelosRESUMO
INTRODUCTION: Spontaneous abortion (SAB) affects approximately 10% of clinically recognized pregnancies. Fetal trophobalst invasion and remodeling of maternal spiral arteries is reported to be dependent on crosstalk between HLA-C/HLA-G expressed on extra villous trophoblast (EVTs)and Killer cell Immunoglobin like receptors (KIRs) of decidual NK (dNK). Immune dysfunction in decidua contributes to early miscarriage. METHODOLOGY: The study used mother neonate paired cord blood and term placenta samples (n = 46), elective abortus (n = 17,gestational age = 10-12 weeks of pregnancy) and SAB abortus (n = 24, gestational age = 12-15 weeks of pregnancy) for HLA-G, KIR2D and HLA-C. In addition, term placenta was collected from women with history of spontaneous pregnancy loss (n = 24) and women with history of live birth (n = 32). SSP-PCR was used for genotyping, RT-PCR for gene expression, copy number variation (CNVs) and HLA-C allotyping and ELISA for protein expression studies. RESULTS: Membrane bound HLA-G4 isoform proportion was higher 39.28%, p = 0.02) in term placenta. SAB abortus had higher proportion of HLA-G3 (50%),while elective abortus exhibited higher proportion of soluble isoforms (HLA-G5, = 5.9, HLA-G6 = 5.9%, HLA-G7 = 11.8%). Higher inhibitory KIR2DL1 content and copy numbers with lower HLA-C2 in SAB contrasted with higher copy numbers of KIR2DS1(p = 0.001), KIR2DS1+/2DL1+- HLA-C2 combined genotype in healthy placenta. Elevated KIR2D protein levels (p = 0.001), and concurrently, HLA-C levels were upregulated in healthy placenta. CONCLUSION: Our data supports lower cognate receptor ligand KIR2DS1+/2DL1+ HLA-C2 together with predominance of HLA-G3 isoform in SAB as confounding factors in spontaneous pregnancy loss. HLA-G isoforms and expression differed between first trimester abortus and term placenta suggesting temporal modulation and marks novelty of the study.