HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity
The novel SARS-CoV-2 coronavirus infection has become a global health concern, causing the COVID-19 pandemic. The disease symptoms and outcomes depend on the host immunity, in which the human leukocyte antigen (HLA) molecules play a distinct role. The HLA alleles have an inter-population variability...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.769900/full |
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| author | Anahit Hovhannisyan Anahit Hovhannisyan Vergine Madelian Sevak Avagyan Mihran Nazaretyan Armine Hyussyan Alina Sirunyan Rubina Arakelyan Zorayr Manukyan Levon Yepiskoposyan Karine R. Mayilyan Frieda Jordan |
| author_facet | Anahit Hovhannisyan Anahit Hovhannisyan Vergine Madelian Sevak Avagyan Mihran Nazaretyan Armine Hyussyan Alina Sirunyan Rubina Arakelyan Zorayr Manukyan Levon Yepiskoposyan Karine R. Mayilyan Frieda Jordan |
| author_sort | Anahit Hovhannisyan |
| collection | DOAJ |
| description | The novel SARS-CoV-2 coronavirus infection has become a global health concern, causing the COVID-19 pandemic. The disease symptoms and outcomes depend on the host immunity, in which the human leukocyte antigen (HLA) molecules play a distinct role. The HLA alleles have an inter-population variability, and understanding their link to the COVID-19 in an ethnically distinct population may contribute to personalized medicine. The present study aimed at detecting associations between common HLA alleles and COVID-19 susceptibility and severity in Armenians. In 299 COVID-19 patients (75 asymptomatic, 102 mild/moderate, 122 severe), the association between disease severity and classic HLA-I and II loci was examined. We found that the advanced age, male sex of patients, and sex and age interaction significantly contributed to the severity of the disease. We observed that an age-dependent effect of HLA-B*51:01 carriage [odds ratio (OR)=0.48 (0.28-0.80), Pbonf <0.036] is protective against severe COVID-19. Contrary, the HLA-C*04:01 allele, in a dose-dependent manner, was associated with a significant increase in the disease severity [OR (95% CI) =1.73 (1.20-2.49), Pbonf <0.021] and an advancing age (P<0.013). The link between HLA-C*04:01 and age was secondary to a stronger association between HLA-C*04:01 and disease severity. However, HLA-C*04:01 exerted a sex-dependent differential distribution between clinical subgroups [females: P<0.0012; males: P=0.48]. The comparison of HLA-C*04:01 frequency between subgroups and 2,781 Armenian controls revealed a significant incidence of HLA-C*04:01 deficiency in asymptomatic COVID-19. HLA-C*04:01 homozygous genotype in patients blueprinted a decrease in heterozygosity of HLA-B and HLA class-I loci. In HLA-C*04:01 carriers, these changes translated to the SARS-CoV-2 peptide presentation predicted inefficacy by HLA-C and HLA class-I molecules, simultaneously enhancing the appropriate HLA-B potency. In patients with clinical manifestation, due to the high prevalence of HLA-C*04:01, these effects provided a decrease of the HLA class-I heterozygosity and an ability to recognize SARS-CoV-2 peptides. Based on our observations, we developed a prediction model involving demographic variables and HLA-C*04:01 allele for the identification of potential cases with the risk of hospitalization (the area under the curve (AUC) = 86.2%) or severe COVID-19 (AUC =71%). |
| first_indexed | 2024-04-11T19:35:36Z |
| format | Article |
| id | doaj.art-dc6a8d0c0f0a4fe5ac2fb9a13c8a1e95 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T19:35:36Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dc6a8d0c0f0a4fe5ac2fb9a13c8a1e952022-12-22T04:06:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-02-011310.3389/fimmu.2022.769900769900HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 SeverityAnahit Hovhannisyan0Anahit Hovhannisyan1Vergine Madelian2Sevak Avagyan3Mihran Nazaretyan4Armine Hyussyan5Alina Sirunyan6Rubina Arakelyan7Zorayr Manukyan8Levon Yepiskoposyan9Karine R. Mayilyan10Frieda Jordan11Institute of Molecular Biology, National Academy of Sciences, Yerevan, ArmeniaRussian-Armenian University, Yerevan, ArmeniaArmenian Bone Marrow Donor Registry Charitable Trust, Yerevan, ArmeniaArmenian Bone Marrow Donor Registry Charitable Trust, Yerevan, ArmeniaArmenian Bone Marrow Donor Registry Charitable Trust, Yerevan, ArmeniaArmenian Bone Marrow Donor Registry Charitable Trust, Yerevan, ArmeniaArmenian Bone Marrow Donor Registry Charitable Trust, Yerevan, ArmeniaClinSoft Armenia, Yerevan, ArmeniaClinStat Group, Lexington, MA, United StatesRussian-Armenian University, Yerevan, ArmeniaInstitute of Molecular Biology, National Academy of Sciences, Yerevan, ArmeniaArmenian Bone Marrow Donor Registry Charitable Trust, Yerevan, ArmeniaThe novel SARS-CoV-2 coronavirus infection has become a global health concern, causing the COVID-19 pandemic. The disease symptoms and outcomes depend on the host immunity, in which the human leukocyte antigen (HLA) molecules play a distinct role. The HLA alleles have an inter-population variability, and understanding their link to the COVID-19 in an ethnically distinct population may contribute to personalized medicine. The present study aimed at detecting associations between common HLA alleles and COVID-19 susceptibility and severity in Armenians. In 299 COVID-19 patients (75 asymptomatic, 102 mild/moderate, 122 severe), the association between disease severity and classic HLA-I and II loci was examined. We found that the advanced age, male sex of patients, and sex and age interaction significantly contributed to the severity of the disease. We observed that an age-dependent effect of HLA-B*51:01 carriage [odds ratio (OR)=0.48 (0.28-0.80), Pbonf <0.036] is protective against severe COVID-19. Contrary, the HLA-C*04:01 allele, in a dose-dependent manner, was associated with a significant increase in the disease severity [OR (95% CI) =1.73 (1.20-2.49), Pbonf <0.021] and an advancing age (P<0.013). The link between HLA-C*04:01 and age was secondary to a stronger association between HLA-C*04:01 and disease severity. However, HLA-C*04:01 exerted a sex-dependent differential distribution between clinical subgroups [females: P<0.0012; males: P=0.48]. The comparison of HLA-C*04:01 frequency between subgroups and 2,781 Armenian controls revealed a significant incidence of HLA-C*04:01 deficiency in asymptomatic COVID-19. HLA-C*04:01 homozygous genotype in patients blueprinted a decrease in heterozygosity of HLA-B and HLA class-I loci. In HLA-C*04:01 carriers, these changes translated to the SARS-CoV-2 peptide presentation predicted inefficacy by HLA-C and HLA class-I molecules, simultaneously enhancing the appropriate HLA-B potency. In patients with clinical manifestation, due to the high prevalence of HLA-C*04:01, these effects provided a decrease of the HLA class-I heterozygosity and an ability to recognize SARS-CoV-2 peptides. Based on our observations, we developed a prediction model involving demographic variables and HLA-C*04:01 allele for the identification of potential cases with the risk of hospitalization (the area under the curve (AUC) = 86.2%) or severe COVID-19 (AUC =71%).https://www.frontiersin.org/articles/10.3389/fimmu.2022.769900/fullCOVID-19 severityHLA classical genesArmenian populationHLA-I heterozygosityaffinity to SARS-CoV-2HLA-C*04:01 |
| spellingShingle | Anahit Hovhannisyan Anahit Hovhannisyan Vergine Madelian Sevak Avagyan Mihran Nazaretyan Armine Hyussyan Alina Sirunyan Rubina Arakelyan Zorayr Manukyan Levon Yepiskoposyan Karine R. Mayilyan Frieda Jordan HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity Frontiers in Immunology COVID-19 severity HLA classical genes Armenian population HLA-I heterozygosity affinity to SARS-CoV-2 HLA-C*04:01 |
| title | HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity |
| title_full | HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity |
| title_fullStr | HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity |
| title_full_unstemmed | HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity |
| title_short | HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity |
| title_sort | hla c 04 01 affects hla class i heterozygosity and predicted affinity to sars cov 2 peptides and in combination with age and sex of armenian patients contributes to covid 19 severity |
| topic | COVID-19 severity HLA classical genes Armenian population HLA-I heterozygosity affinity to SARS-CoV-2 HLA-C*04:01 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.769900/full |
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