Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19
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 genot...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.641900/full |
| _version_ | 1831636317663920128 |
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| author | Maxim Shkurnikov Stepan Nersisyan Tatjana Jankevic Alexei Galatenko Alexei Galatenko Ivan Gordeev Ivan Gordeev Valery Vechorko Alexander Tonevitsky Alexander Tonevitsky |
| author_facet | Maxim Shkurnikov Stepan Nersisyan Tatjana Jankevic Alexei Galatenko Alexei Galatenko Ivan Gordeev Ivan Gordeev Valery Vechorko Alexander Tonevitsky Alexander Tonevitsky |
| author_sort | Maxim Shkurnikov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T06:30:51Z |
| format | Article |
| id | doaj.art-8a8f86516b9d438c84bf94090da4915b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T06:30:51Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8a8f86516b9d438c84bf94090da4915b2022-12-21T20:32:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011210.3389/fimmu.2021.641900641900Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19Maxim Shkurnikov0Stepan Nersisyan1Tatjana Jankevic2Alexei Galatenko3Alexei Galatenko4Ivan Gordeev5Ivan Gordeev6Valery Vechorko7Alexander Tonevitsky8Alexander Tonevitsky9Faculty of Biology and Biotechnology, HSE University, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaCenter for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaFaculty of Mechanics and Mathematics, Lomonosov Moscow State University, Moscow, RussiaCenter for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, RussiaO.M. Filatov City Clinical Hospital, Moscow, RussiaO.M. Filatov City Clinical Hospital, Moscow, RussiaFaculty of Biology and Biotechnology, HSE University, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaHuman 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.641900/fullHLA class IMHC class ICOVID-19SARS-CoV-2peptide presentation |
| spellingShingle | Maxim Shkurnikov Stepan Nersisyan Tatjana Jankevic Alexei Galatenko Alexei Galatenko Ivan Gordeev Ivan Gordeev Valery Vechorko Alexander Tonevitsky Alexander Tonevitsky Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19 Frontiers in Immunology HLA class I MHC class I COVID-19 SARS-CoV-2 peptide presentation |
| title | Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19 |
| title_full | Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19 |
| title_fullStr | Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19 |
| title_full_unstemmed | Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19 |
| title_short | Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19 |
| title_sort | association of hla class i genotypes with severity of coronavirus disease 19 |
| topic | HLA class I MHC class I COVID-19 SARS-CoV-2 peptide presentation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.641900/full |
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