RESUMO
The new allele HLA-DRB1*16:02:10 showed one synonymous nucleotide difference with HLA-DRB1*16:02:01:01 in codon 58.
Assuntos
Medula Óssea , Doadores de Tecidos , Alelos , Sequência de Bases , Cadeias HLA-DRB1/genética , Teste de Histocompatibilidade , HumanosRESUMO
Human leukocyte antigen (HLA) class I molecules play a crucial role in the development of a specific immune response to viral infections by presenting viral peptides at the cell surface where they will be further recognized by T cells. In the present manuscript, we explored whether HLA class I genotypes can be associated with the critical course of Coronavirus Disease-19 by searching possible connections between genotypes of deceased patients and their age at death. HLA-A, HLA-B, and HLA-C genotypes of n = 111 deceased patients with COVID-19 (Moscow, Russia) and n = 428 volunteers were identified with next-generation sequencing. Deceased patients were split into two groups according to age at the time of death: n = 26 adult patients aged below 60 and n = 85 elderly patients over 60. With the use of HLA class I genotypes, we developed a risk score (RS) which was associated with the ability to present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides by the HLA class I molecule set of an individual. The resulting RS was significantly higher in the group of deceased adults compared to elderly adults [p = 0.00348, area under the receiver operating characteristic curve (AUC ROC = 0.68)]. In particular, presence of HLA-A*01:01 allele was associated with high risk, while HLA-A*02:01 and HLA-A*03:01 mainly contributed to low risk. The analysis of patients with homozygosity strongly highlighted these results: homozygosity by HLA-A*01:01 accompanied early deaths, while only one HLA-A*02:01 homozygote died before 60 years of age. Application of the constructed RS model to an independent Spanish patients cohort (n = 45) revealed that the score was also associated with the severity of the disease. The obtained results suggest the important role of HLA class I peptide presentation in the development of a specific immune response to COVID-19.
Assuntos
COVID-19/imunologia , COVID-19/mortalidade , Genótipo , Antígenos HLA-A/genética , SARS-CoV-2/genética , Índice de Gravidade de Doença , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alelos , COVID-19/patologia , COVID-19/virologia , Estudos de Coortes , Feminino , Frequência do Gene , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
HLA-C*15:227 differs from HLA-C*15:02:01:01 by a single nonsynonymous change (368A â G Tyrosine 99 to Cysteine).
Assuntos
COVID-19/genética , Antígenos HLA-C/genética , Polimorfismo de Nucleotídeo Único , Alelos , COVID-19/imunologia , Bases de Dados Genéticas , Antígenos HLA-C/classificação , Sequenciamento de Nucleotídeos em Larga Escala , Teste de Histocompatibilidade , Humanos , Federação Russa , Análise de Sequência de DNA , Terminologia como AssuntoRESUMO
The new allele HLA-DQB1*05:02:24 showed one synonymous nucleotide difference with HLA-DQB1*05:02:01:01 in codon 140.
Assuntos
Medula Óssea , Alelos , Cadeias beta de HLA-DQ/genética , Humanos , Federação RussaRESUMO
The new allele HLA-A*11:382N showed one nucleotide difference with HLA-A*11:01:01:01 at codon 254 (nonsense mutation).
