scholarly journals Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Austin Nguyen ◽  
Julianne K. David ◽  
Sean K. Maden ◽  
Mary A. Wood ◽  
Benjamin R. Weeder ◽  
...  

ABSTRACT Genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen A [HLA-A], -B, and -C genes) may affect susceptibility to and severity of the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). We performed a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across 145 HLA-A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explored the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome was successfully sampled and was represented by a diversity of HLA alleles. However, we found that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2, suggesting that individuals with this allele may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS (M. Lin, H.-T. Tseng, J. A. Trejaut, H.-L. Lee, et al., BMC Med Genet 4:9, 2003, https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-4-9). Conversely, we found that HLA-B*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting that it could enable cross-protective T-cell-based immunity. Finally, we reported global distributions of HLA types with potential epidemiological ramifications in the setting of the current pandemic. IMPORTANCE Individual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of severity of viral disease in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.

Author(s):  
Austin Nguyen ◽  
Julianne K. David ◽  
Sean K. Maden ◽  
Mary A. Wood ◽  
Benjamin R. Weeder ◽  
...  

ABSTRACTGenetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen [HLA] A, B, and C) may affect susceptibility to and severity of severe acute respiratory syndrome 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). We execute a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across 145 HLA -A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explore the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome is successfully sampled and presented by a diversity of HLA alleles. However, we found that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2, suggesting individuals with this allele may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS (1). Conversely, we found that HLA-B*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting it could enable cross-protective T-cell based immunity. Finally, we report global distributions of HLA types with potential epidemiological ramifications in the setting of the current pandemic.IMPORTANCEIndividual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of viral severity in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.


2018 ◽  
Vol 44 (1) ◽  
pp. 1-8
Author(s):  
Sharmin Sultana ◽  
Shahina Tabassum ◽  
Afzalun Nessa

Human leukocyte antigen (HLA) are cell surface glycoproteins encoded by Major Histocompatibility Complex (MHC) geneof human genome. HLA antigen frequency and haplotype distribution are useful for determining disease associations, origin, migration and genetic relationships between populations and predicting the outcome of transplantation. Thus, the present study was carried outto identify HLA class I (HLA-A and HLA-B) antigen and haplotype distribution among a selected Bangladeshi population. This retrospective study was conducted among 1070 individuals who were referred by cliniciansfor HLA typing at the Tissue Typing Laboratory of the Department of Virology, Bangabandhu Sheikh Mujib Medical University (BSMMU) during the period 2009 to 2011. For HLA typing, Blood was collected in heparin containing tube and the laboratory tests were performed by the microlymphocytotoxicity technique according to manufacturer’s instructions.Out of 19 HLA-A and 37HLA-B antigens tested, a total of 19/19 and 36/37 antigens were detectedrespectively in this study. The most frequent antigens of HLA-A and HLA-B detected were A11 (25.4%), A24 (16.6%), B75 (18.1%) and B35 (11.3%). The least antigen frequency detected for HLA-A locus were A69 (0.09%), A26 (0.28%), A34 (0.28%), while for HLA-B locus were B81 (0.09%) and B56 (0.09%). Among the HLA-A and HLA-B antigens, some alleles were found to be homozygote such as A11 (4.0%), A2 (2.7%), A24 (2.1%) andB75 (2.4%), B35 (1.8%), and B44 (1.4%) respectively. The most frequent haplotype in the study populationwereA11: B75 (4.9%). The most frequent antigens of HLA-A and HLA-B detected were A11 (25.4%), B75 (18.1%) respectively. The distribution of HLA haplotypes among the study population indicates that it has the influence of Oriental and Asian populations. Thus, this study will be helpful to provide valuable information for population genetics and HLA disease association analysis.Bangladesh Med Res Counc Bull 2018; 44(1):01-08


2020 ◽  
Vol 45 (5) ◽  
pp. 587-592
Author(s):  
Cigdem Kekik Cinar ◽  
Kadir Demir ◽  
Sonay Temurhan ◽  
Filiz Akyuz ◽  
Binnur Pinarbasi ◽  
...  

AbstractObjectivesWe aimed to determine Human Leukocyte Antigen (HLA)-DRB1, DQB1, and MHC Class I related chain A (MICA) genotypes in patients with ulcerative colitis.MethodsHLA-DRB1, HLA-DQB1, MICA genotyping of patient (n:85) and controls (n:100) were performed by PCR-SSO Luminex (One Lambda genotyping kit).ResultsWe found significantly higher DRB1*01 (p:0.022, OR:0.23, CI:0.06–0.8) and MICA*0002/20/55 (p:0.03, OR:0.53, CI:0.29–0.93) alleles in control group whereas DRB1*14 (p:0.04, OR:2.25, CI:1–5.08), DRB1*15 (p:<0.0001, OR:4.54, CI:2.09–9.88) and MICA*0004 (p:0.01, OR:2.84, CI:1.2–6.7) alleles were higher in patient group.ConclusionsThe present study will inform the MICA and HLA genotypes about the protective (DRB1*01, MICA*0002/20/55) or susceptible (DRB1*14, DRB1*15, MICA*0004) alleles of the disease and helps the literature on Turkish patients with ulcerative colitis.


2017 ◽  
Author(s):  
Chang Liu ◽  
Fangzhou Xiao ◽  
Jessica Hoisington-Lopez ◽  
Kathrin Lang ◽  
Philipp Quenzel ◽  
...  

ABSTRACTOxford Nanopore Technologies’ MinION has expanded the current DNA sequencing toolkit by delivering long read lengths and extreme portability. The MinION has the potential to enable expedited point-of-care human leukocyte antigen (HLA) typing, an assay routinely used to assess the immunological compatibility between organ donors and recipients, but the platform’s high error rate makes it challenging to type alleles with clinical-grade accuracy. Here, we developed and validated Athlon, an algorithm that iteratively scores nanopore reads mapped to a hierarchical database of HLA alleles to arrive at a consensus diploid genotype; Athlon achieved a 100% accuracy in class I HLA typing at high resolution.


2019 ◽  
Vol 20 (19) ◽  
pp. 4875 ◽  
Author(s):  
Vanegas ◽  
Galindo ◽  
Páez-Gutiérrez ◽  
González-Acero ◽  
Medina-Valderrama ◽  
...  

Hematopoietic progenitor cell (HPC) transplantation is a treatment option for malignant and nonmalignant diseases. Umbilical cord blood (UCB) is an important HPC source, mainly for pediatric patients. It has been demonstrated that human leukocyte antigen (HLA) matching and cell dose are the most important features impacting clinical outcomes. However, UCB matching is performed using low resolution HLA typing and it has been demonstrated that the unnoticed mismatches negatively impact the transplant. Since we found differences in CD34+ viability after thawing of UCB units matched for two different patients (p = 0.05), we presumed a possible association between CD34+ cell viability and HLA. We performed a multivariate linear model (n = 67), comprising pre-cryopreservation variables and high resolution HLA genotypes separately. We found that pre-cryopreservation red blood cells (RBC), granulocytes, and viable CD34+ cell count significantly impacted CD34+ viability after thawing, along with HLA-B or -C (R2 = 0.95, p = 0.01; R2 = 0.56, p = 0.007, respectively). Although HLA-B*40:02 may have a negative impact on CD34+ cell viability, RBC depletion significantly improves it.


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