Association of HLA class I genotypes with age at death of COVID-19 patients

AbstractBackgroundHLA class I molecules play a crucial role in the development of a specific immune response to viral infections by presenting viral peptides to cell surface where they will be further recognized by T cells. In the present manuscript we explored whether HLA class I genotype can be associated with critical course of COVID-19 by searching possible connections between genotypes of deceased patients and their age at death.Methods and FindingsHLA-A, HLA-B and HLA-C genotypes of n = 111 deceased patients with COVID-19 (Moscow, Russia) and n = 428 volunteers were identified with targeted next-generation sequencing. Deceased patients were splitted into two groups according to age at death: n = 26 adult patients with age at death below 60 completed years (inclusively) and n = 85 elderly patients over 60. With the use of HLA class I genotypes we developed a risk score which is associated with the ability to present SARS-CoV-2 peptides by an individual’s HLA class I molecule set. The resulting risk score was significantly higher in the group of deceased adults compared to elderly adults (p = 0.00348, 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 the low risk group. The analysis of homozygous patients highlighted the results even stronger: homozygosity by HLA-A*01:01 mainly accompanied early deaths, while only one HLA-A*02:01 homozygote died before 60.ConclusionsThe obtained results suggest the important role of HLA class I peptide presentation in the development of a specific immune response to COVID-19. While prediction of age at death by HLA class I genotype had a reliable performance, involvement of HLA class II genotype can make it even higher in the future studies.

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Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19

Frontiers in Immunology ◽

10.3389/fimmu.2021.641900 ◽

2021 ◽

Vol 12 ◽

Author(s):

Maxim Shkurnikov ◽

Stepan Nersisyan ◽

Tatjana Jankevic ◽

Alexei Galatenko ◽

Ivan Gordeev ◽

...

Keyword(s):

Immune Response ◽

Viral Infections ◽

Characteristic Curve ◽

Human Leukocyte ◽

Hla Class I ◽

Specific Immune Response ◽

Class I ◽

Leukocyte Antigen ◽

Hla Class I Molecules ◽

Severity Of The Disease

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.

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HLA class I molecules in implantation

Fetal and Maternal Medicine Review ◽

10.1017/s0965539501000444 ◽

2001 ◽

Vol 12 (4) ◽

pp. 299-314

Author(s):

YW Loke ◽

Ashley King

Keyword(s):

Immune Response ◽

Immune System ◽

Research Effort ◽

Hla Class I ◽

Class I ◽

Hla Class I Antigens ◽

Transplantation Immunology ◽

Hla Class I Molecules ◽

Unusual Combination ◽

Clinical Transplantation

Because half its genes are inherited from the father, the embryo during pregnancy has been frequently compared to an allograft transplanted into the maternal uterus. The question why the embryo is, therefore, not rejected by the mother's immune response in the same way as other allografts has still not been satisfactorily answered. Recent investigations indicate that this analogy may not be as close as it initially appears. One major difference is the expression of an unusual combination of HLA class I molecules by the placental trophoblast cells which invade into uterine decidua during implantation. Furthermore, the lymphoid population in the uterus potentially capable of interacting with these trophoblast HLA class I antigens also appears to be unique. These observations have led to the suggestion that implantation might utilise a novel immune system which is different to that seen in clinical transplantation immunology. Much research effort is now directed towards the elucidation of the mechanisms involved and the outcome of this interaction because this is likely to be how implantation is controlled.

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Analysis of transporter associated with antigen presentation (TAP) genes polymorphisms with HIV-1 infection

Molecular and Cellular Biochemistry ◽

10.1007/s11010-019-03649-x ◽

2019 ◽

Vol 464 (1-2) ◽

pp. 65-71 ◽

Cited By ~ 1

Author(s):

Abaineh Munshea Abitew ◽

Ranbir Chander Sobti ◽

Vijay Lakshmi Sharma ◽

Ajay Wanchu

Keyword(s):

Immune Response ◽

Hla Class I ◽

Class I ◽

Control Analysis ◽

Antigenic Peptides ◽

Human Major Histocompatibility Complex ◽

Hla Class I Molecules ◽

Increased Risk ◽

Exon 11 ◽

Hiv 1

AbstractHuman leukocyte antigen (HLA) class I molecules of the human major histocompatibility complex (MHC) play an important role in modulating immune response. HLA class I molecules present antigenic peptides to CD8+ T cells and thereby play a role in the immune surveillance of cells infected with viruses. TAP1 and TAP2 are MHC-II-encoded genes necessary for the generation of a cellular immune response and polymorphism of these genes can influence the specificity of peptides preferentially presented by the MHC class I molecules and the outcome of the immune response. Several studies implicated genetic variation in TAP genes to various immune-mediated and infectious diseases. To determine the correlation between HIV-1 infection and the TAP1 and TAP2 genes polymorphisms, we performed PCR–RFLP assay of these genes in 500 HIV-1 seropositives and the matched seronegative individuals. Statistical analysis of the data disclosed no correlation between TAP1 (C/T intron 7) gene polymorphism and HIV-1/AIDS disease. However, the current results demonstrated that the heterozygous A/G [OR (95% CI) 1.39 (1.06–1.83), P = 0.0171] and homozygous G/G [OR (95% CI) 3.38(1.56–7.46), P = 0.0010] variants of TAP2 (A/G exon 11) (T665A) gene are positively associated with an increased risk of HIV-1/AIDS infection. This case–control analysis might suggest a possible role of TAP2 (A/G exon 11) (T665A) gene in the susceptibility to HIV-1 infection and disease outcome among North Indian patients.

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Association of HLA class I type with prevalence and outcome of patients with acute myeloid leukemia and mutated nucleophosmin

10.1101/411645 ◽

2018 ◽

Author(s):

Kateřina Kuželová ◽

Barbora Brodská ◽

Johannes Schetelig ◽

Christoph Röllig ◽

Zdeněk Ráčil ◽

...

Keyword(s):

Immune Response ◽

Acute Myeloid Leukemia ◽

T Cell ◽

Myeloid Leukemia ◽

Hla Class I ◽

Class I ◽

Cell Mediated Immunity ◽

Hla Class I Molecules ◽

Cell Mediated Immune Response ◽

Acute Myeloid

AbstractAcute myeloid leukemia with mutated nucleophosmin (NPMc+ AML) forms a distinct AML subgroup with better prognosis which can potentially be associated with immune response against the mutated nucleophosmin (NPM). As the T-cell-mediated immunity involves antigen presentation on HLA class I molecules, we hypothesized that individuals with suitable HLA type could be less prone to develop NPMc+ AML. We compared HLA class I distribution in NPMc+ AML patient cohort (398 patients from 5 centers) with the HLA allele frequencies of the caucasian population and found HLA-A*02, B*07, B*40 and C*07 underrepresented in the NPMc+ AML group. Presence of B*07 or C*07:01 antigen was associated with better survival in patients without concomitant FLT3 internal tandem duplication. Candidate NPM-derived immunopeptides were found for B*40 and B*07 using prediction software tools. Our findings suggest that a T-cell-mediated immune response could actually explain better prognosis of NPMc+ patients and provide a rationale for attempts to explore the importance of immunosuppressive mechanisms in this AML subgroup.

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