Concurrent typing of over 4000 samples by long-range PCR amplicon-based NGS and rSSO revealed the need to verify NGS typing for HLA allelic dropouts

Kong, Denice; Lee, Nancy; Cruz, Imma Donna Dela; Dames, Charlyn; Maruthamuthu, Stalinraja; Golden, Todd; Rajalingam, Raja

doi:10.1016/j.humimm.2021.04.008

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…The control samples were HLA typed using a commercially available Sequence-Specific Oligonucleotide hybridization kit (LABType ® SSO, One Lambda, Canoga Park, CA). We described the KIR genotyping ( Sun et al, 2021 ) and HLA genotyping protocols by NGS ( Kong et al, 2021 ) and SSO ( Sun et al, 2021 ) elaborately in our previous publications.…”

Section: Methodsmentioning

confidence: 99%

Individualized Constellation of Killer Cell Immunoglobulin-Like Receptors and Cognate HLA Class I Ligands that Controls Natural Killer Cell Antiviral Immunity Predisposes COVID-19

et al. 2022

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Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causes coronavirus disease-2019 (COVID-19) in some individuals, while the majority remain asymptomatic. Natural killer (NK) cells play an essential role in antiviral defense. NK cell maturation and function are regulated mainly by highly polymorphic killer cell immunoglobulin-like receptors (KIR) and cognate HLA class I ligands. Herein, we tested our hypothesis that the individualized KIR and HLA class I ligand combinations that control NK cell function determine the outcome of SARS-CoV-2 infection.Methods: We characterized KIR and HLA genes in 200 patients hospitalized for COVID-19 and 195 healthy general population controls.Results: The KIR3DL1+HLA-Bw4+ [Odds ratio (OR) = 0.65, p = 0.03] and KIR3DL2+HLA-A3/11+ (OR = 0.6, p = 0.02) combinations were encountered at significantly lower frequency in COVID-19 patients than in the controls. Notably, 40% of the patients lacked both of these KIR+HLA+ combinations compared to 24.6% of the controls (OR = 2.04, p = 0.001). Additionally, activating receptors KIR2DS1+KIR2DS5+ are more frequent in patients with severe COVID-19 than patients with mild disease (OR = 1.8, p = 0.05). Individuals carrying KIR2DS1+KIR2DS5+ genes but missing either KIR3DL1+HLA-Bw4+ combination (OR = 1.73, p = 0.04) or KIR3DL2+HLA-A3/11+ combination (OR = 1.75, p = 0.02) or both KIR3DL1+HLA-Bw4+ and KIR2DL2+HLA-A3/11+ combinations (OR = 1.63, p = 0.03) were more frequent in the COVID-19 cohort compared to controls.Conclusions: The absence of KIR3DL1+HLA-Bw4+ and KIR3DL2+HLA-A3/11+ combinations presumably yields inadequate NK cell maturation and reduces anti-SARS-CoV-2 defense, causing COVID-19. An increased frequency of KIR2DS1+KIR2DS5+ in severe COVID-19 patients suggests vigorous NK cell response triggered via these activating receptors and subsequent production of exuberant inflammatory cytokines responsible for severe COVID-19. Our results demonstrate that specific KIR-HLA combinations that control NK cell maturation and function are underlying immunogenetic variables that determine the dual role of NK cells in mediating beneficial antiviral and detrimental pathologic action. These findings offer a framework for developing potential host genetic biomarkers to distinguish individuals prone to COVID-19.

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Section: Methodsmentioning

confidence: 99%

Individualized Constellation of Killer Cell Immunoglobulin-Like Receptors and Cognate HLA Class I Ligands that Controls Natural Killer Cell Antiviral Immunity Predisposes COVID-19

et al. 2022

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“…However, it may pose challenges such as allelic dropouts and limited resolution for capturing all HLA genetic variations, potentially leading to an incomplete characterization of HLA alleles. Balancing these advantages and limitations is crucial for making informed decisions regarding the suitability of this method for specific HLA typing applications [ 43 , 70 , 71 ]. Hybrid capture-based NGS for HLA typing has distinct pros and cons.…”

Section: Next-generation Sequencingmentioning

confidence: 99%

“…Verification can be Enhancing Transplantation Outcomes: Advances in HLA Typing challenging, requiring careful validation when reconciling with lower-resolution methods. Choosing hybrid capturebased NGS for HLA typing should consider these factors based on specific study or clinical needs and constraints [70,71].…”

Section: Next-generation Sequencingmentioning

confidence: 99%

Advancements in HLA Typing Techniques and Their Impact on Transplantation Medicine

Geo,

Ameen,

Al Shemmari

et al. 2024

Med Princ Pract

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HLA typing serves as a standard practice in hematopoietic stem cell transplantation to ensure compatibility between donors and recipients, preventing the occurrence of allograft rejection and graft-versus-host disease. Conventional laboratory methods that have been widely employed in the past few years, including sequence-specific primer PCR and sequencing-based typing (SBT), currently face the risk of becoming obsolete. This risk stems not only from the extensive diversity within HLA genes but also from the rapid advancement of next-generation sequencing and third-generation sequencing technologies. Third-generation sequencing systems like single-molecule real-time (SMRT) sequencing and Oxford Nanopore (ONT) sequencing have the capability to analyze long-read sequences that span entire intronic-exonic regions of HLA genes, effectively addressing challenges related to HLA ambiguity and the phasing of multiple short-read fragments. The growing dominance of these advanced sequencers in HLA typing is expected to solidify further through ongoing refinements, cost reduction, and error rate minimization. This review focuses on hematopoietic stem cell transplantation (HSCT) and explores prospective advancements and application of HLA DNA typing techniques. It explores how the adoption of third-generation sequencing technologies can revolutionize the field by offering improved accuracy, reduced ambiguity, and enhanced assessment of compatibility in HSCT. Embracing these cutting-edge technologies is essential to advancing the success rates and outcomes of hematopoietic stem cell transplantation. This review underscores the importance of staying at the forefront of HLA typing techniques to ensure the best possible outcomes for patients undergoing HSCT.

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A national proficiency scheme for human leucocyte antigen typing by next-generation sequencing

Lin

Zhang

2022

Clinica Chimica Acta

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Concurrent typing of over 4000 samples by long-range PCR amplicon-based NGS and rSSO revealed the need to verify NGS typing for HLA allelic dropouts

Cited by 6 publications

References 35 publications

Individualized Constellation of Killer Cell Immunoglobulin-Like Receptors and Cognate HLA Class I Ligands that Controls Natural Killer Cell Antiviral Immunity Predisposes COVID-19

Individualized Constellation of Killer Cell Immunoglobulin-Like Receptors and Cognate HLA Class I Ligands that Controls Natural Killer Cell Antiviral Immunity Predisposes COVID-19

Advancements in HLA Typing Techniques and Their Impact on Transplantation Medicine

A national proficiency scheme for human leucocyte antigen typing by next-generation sequencing

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