The role of the HLA allelic repertoire on the clinical severity of COVID-19 in Canadians, living in the Saskatchewan province

Kakodkar, Pramath; Dokouhaki, Pouneh; Wu, Fang; Shavadia, Jay; Nair, Revathi; Webster, Destinie; Sawyer, Terry; Huan, Tao; Mostafa, Ahmed

doi:10.1016/j.humimm.2023.01.003

Cited by 2 publications

(5 citation statements)

References 34 publications

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“…DNA extraction was performed, as previously described by Kakodkar et al (2023 ). Briefly, DNA extractions were prepared by QIAGEN, using the BioRobot ® EZ1 system (QIAGEN, Toronto, Canada) and EZ1 DNA Blood 350 μL Kit (Catalog 951,054), using whole blood collected in acid citrate dextrose tubes and isolated cell fractions.…”

Section: Methodsmentioning

confidence: 99%

Validation of next-generation sequencing-based chimerism testing for accurate detection and monitoring of engraftment in hematopoietic stem cell transplantation

Kakodkar,

Zhao,

Pan

et al. 2023

Front. Genet.

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Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a life-saving treatment for various hematological disorders. The success of allo-HSCT depends on the engraftment of donor cells and the elimination of recipient cells monitored through chimerism testing. We aimed to validate a next-generation sequencing (NGS)-based chimerism assay for engraftment monitoring and to emphasize the importance of including the most prevalent cell subsets in proficiency testing (PT) programs. We evaluated the analytical performance of NGS-based chimerism testing (AlloSeq-HCT and CareDx) with a panel of targeted 202 informative single-nucleotide polymorphisms (SNPs) (i.e., linearity and precision, analytical sensitivity and specificity, system accuracy, and reproducibility). We further compared the performance of our NGS panel with conventional short tandem repeat (STR) analysis in unfractionated whole blood and cell-subset-enriched CD3 and CD66. Our NGS-based chimerism monitoring assay has an impressive detection limit (0.3% host DNA) for minor alleles and analytical specificity (99.9%). Pearson’s correlation between NGS- and STR-based chimerism monitoring showed a linear relationship with a slope of 0.8 and r = 0.973. The concordance of allo-HSCT patients using unfractionated whole blood, CD3, and CD66 was 0.95, 0.96, and 0.54, respectively. Utilization of CD3+ cell subsets for mixed chimerism detection yielded an average of 7.3 ± 7-fold higher donor percentage detection compared to their corresponding unfractionated whole blood samples. The accuracy of the NGS assay achieved a concordance of 98.6% on blinded external quality control STR samples. The reproducibility series showed near 100% concordance with respect to inter-assay, inter-tech, inter-instrument, cell flow kits, and AlloSeq-HCT software versions. Our study provided robust validation of NGS-based chimerism testing for accurate detection and monitoring of engraftment in allo-HSCT patients. By incorporating the cell subsets (CD3 and CD66), the sensitivity and accuracy of engraftment monitoring are significantly improved, making them an essential component of any PT program. Furthermore, the implementation of NGS-based chimerism testing shows potential to streamline high-volume transplant services and improve clinical outcomes by enabling early relapse detection and guiding timely interventions.

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Section: Methodsmentioning

confidence: 99%

Validation of next-generation sequencing-based chimerism testing for accurate detection and monitoring of engraftment in hematopoietic stem cell transplantation

Kakodkar,

Zhao,

Pan

et al. 2023

Front. Genet.

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“…The HLA is a highly polymorphic system that exhibits significant regional variations. Due to the high polymorphism of the HLA molecule and its ethnic dependency, data on HLA allele frequencies can vary widely between populations and sometimes yield conflicting results 20,21 . For example, an allele that confers protection in one population may be associated with severe disease in another population.…”

Section: Hla Immune Response and Susceptibility To Covid‐19mentioning

confidence: 99%

“…These differences can be attributed to a variety of factors including social constructions, cultural identity, and behavioral patterns that are common across different ethnic groups. Additionally, genetic variations have a significant role in the spread of viruses and the severity of diseases 21,44 . In the last decade, a critical technique known as genome‐wide association study (GWA or GWAS) has emerged to investigate the relationship between genetic backgrounds and various phenotypes.…”

Section: Hla Alleles Distribution In Countriesmentioning

confidence: 99%

“…Due to the high polymorphism of the HLA molecule and its ethnic dependency, data on HLA allele frequencies can vary widely between populations and sometimes yield conflicting results. 20 , 21 For example, an allele that confers protection in one population may be associated with severe disease in another population. It is so difficult to confirm obtained results from every study in comparison to the others because of high polymorphism in the HLA molecule and being ethnicity‐related.…”

Section: Hla Immune Response and Susceptibility To ...mentioning

confidence: 99%

“…Additionally, genetic variations have a significant role in the spread of viruses and the severity of diseases. 21 , 44 In the last decade, a critical technique known as genome‐wide association study (GWA or GWAS) has emerged to investigate the relationship between genetic backgrounds and various phenotypes. The GWAS, by identifying clusters of related SNPs, or genomic risk loci, in one population with a continuous characteristic, can show a statistically significant genotype–phenotype association with diseases and traits.…”

Section: Hla Alleles Distribution In Countriesmentioning

confidence: 99%

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The role of HLA genetic variants in COVID‐19 susceptibility, severity, and mortality: A global review

Hoseinnezhad,

Soltani,

Ziarati

et al. 2024

Clinical Laboratory Analysis

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BackgroundThe COVID‐19 pandemic has had a profound global impact, with variations in susceptibility, severity, and mortality rates across different regions. While many factors can contribute to the spread and impact of the disease, specifically human leukocyte antigen (HLA) genetic variants have emerged as potential contributors to COVID‐19 outcomes.MethodsIn this comprehensive narrative review, we conducted a thorough literature search to identify relevant studies investigating the association between HLA genetic variants and COVID‐19 outcomes. Additionally, we analyzed allelic frequency data from diverse populations to assess differences in COVID‐19 incidence and severity.ResultsOur review provides insights into the immunological mechanisms involving HLA‐mediated responses to COVID‐19 and highlights potential research directions and therapeutic interventions. We found evidence suggesting that certain HLA alleles, such as HLA‐A02, may confer a lower risk of COVID‐19, while others, like HLA‐C04, may increase the risk of severe symptoms and mortality. Furthermore, our analysis of allele frequency distributions revealed significant variations among different populations.ConclusionConsidering host genetic variations, particularly HLA genetic variants, is crucial for understanding COVID‐19 susceptibility and severity. These findings have implications for personalized treatment and interventions based on an individual's genetic profile. However, further research is needed to unravel the precise mechanisms underlying the observed associations and explore the potential for targeted therapies or preventive measures based on HLA genetic variants.

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The role of the HLA allelic repertoire on the clinical severity of COVID-19 in Canadians, living in the Saskatchewan province

Cited by 2 publications

References 34 publications

Validation of next-generation sequencing-based chimerism testing for accurate detection and monitoring of engraftment in hematopoietic stem cell transplantation

Validation of next-generation sequencing-based chimerism testing for accurate detection and monitoring of engraftment in hematopoietic stem cell transplantation

The role of HLA genetic variants in COVID‐19 susceptibility, severity, and mortality: A global review

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