Killer‐cell immunoglobulin‐like receptor assessment algorithms in haemopoietic progenitor cell transplantation: current perspectives and future opportunities

Wright, Paul A.

doi:10.1111/tan.13817

Cited by 6 publications

(7 citation statements)

References 95 publications

(172 reference statements)

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“…Counterintuitively, this clinical study ( 75 ) has shown that recipients not lacking the KIR–ligand of the cognate donor experienced better overall survival in leukemia patients, in contradiction with the receptor–ligand model ( 76 ). Nowak et al.…”

Section: Kir Alloreactivity Assessmentmentioning

confidence: 86%

“…also hypothesize that couples predicted as alloreactive by the receptor–ligand model could have lymphocytes remaining largely hyporesponsive to stimulus, as the receptor–ligand model does not take into account donor NK cell education ( 79 ). However, the proportion of favorable couples fitting the educational model is small, meaning that only few D/R couples could benefit ( 76 ).…”

Section: Kir Alloreactivity Assessmentmentioning

confidence: 99%

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KIR in Allogeneic Hematopoietic Stem Cell Transplantation: Need for a Unified Paradigm for Donor Selection

Dhuyser

Aarnink

Pérès³

et al. 2022

Front. Immunol.

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Allogeneic hematopoietic stem cell transplantation (aHSCT) is a lifesaving therapy for hematological malignancies. For years, a fully matched HLA donor was a requisite for the procedure. However, new immunosuppressive strategies have enabled the recruitment of viable alternative donors, particularly haploidentical donors. Over 95% of patients have at least two potential haploidentical donors available to them. To identify the best haploidentical donor, the assessment of new immunogenetic criteria could help. To this end, the clinical benefit of KIR genotyping in aHSCT has been widely studied but remains contentious. This review aims to evaluate the importance of KIR-driven NK cell alloreactivity in the context of aHSCT and explain potential reasons for the discrepancies in the literature. Here, through a non-systematic review, we highlight how the studies in this field and their respective predictive models or scoring strategies could be conceptually opposed, explaining why the role of NK cells remains unclear in aHCST outcomes. We evaluate the limitations of each published prediction model and describe how every scoring strategy to date only partly delivers the requirements for optimally effective NK cells in aHSCT. Finally, we propose approaches toward finding the optimal use of KIR genotyping in aHSCT for a unified criterion for donor selection.

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Section: Kir Alloreactivity Assessmentmentioning

confidence: 86%

Section: Kir Alloreactivity Assessmentmentioning

confidence: 99%

KIR in Allogeneic Hematopoietic Stem Cell Transplantation: Need for a Unified Paradigm for Donor Selection

Dhuyser

Aarnink

Pérès³

et al. 2022

Front. Immunol.

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“…Without ground truth available, without any reason to expect this cohort to deviate from expectations, and considering KIR*IMP's self-reported accuracy, the evidence suggests that KPI's predictions are more accurate than KIR*IMP's in this cohort and specifically that KIR*IMP under called the presence of genes KIR2DS2, KIR2DL2, KIR2DS3, KIR2DL5 and haplotypes cB01~tA01 and cB02~tA01. As reviewed recently by Wright et al, this may be particularly relevant in the context of hematopoietic stem cell transplantation, where some case/control studies claim an important role for these regions (19). There are several potential reasons KIR*IMP's predictions may be less accurate than KPI's.…”

Section: Discussionmentioning

confidence: 99%

Accurate and Efficient KIR Gene and Haplotype Inference From Genome Sequencing Reads With Novel K-mer Signatures

Roe

Kuang

2020

Front. Immunol.

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The killer-cell immunoglobulin-like receptor (KIR) proteins evolve to fight viruses and mediate the body’s reaction to pregnancy. These roles provide selection pressure for variation at both the structural/haplotype and base/allele levels. At the same time, the genes have evolved relatively recently by tandem duplication and therefore exhibit very high sequence similarity over thousands of bases. These variation-homology patterns make it impossible to interpret KIR haplotypes from abundant short-read genome sequencing data at population scale using existing methods. Here, we developed an efficient computational approach for in silico KIR probe interpretation (KPI) to accurately interpret individual’s KIR genes and haplotype-pairs from KIR sequencing reads. We designed synthetic 25-base sequence probes by analyzing previously reported haplotype sequences, and we developed a bioinformatics pipeline to interpret the probes in the context of 16 KIR genes and 16 haplotype structures. We demonstrated its accuracy on a synthetic data set as well as a real whole genome sequences from 748 individuals from The Genome of the Netherlands (GoNL). The GoNL predictions were compared with predictions from SNP-based predictions. Our results show 100% accuracy rate for the synthetic tests and a 99.6% family-consistency rate in the GoNL tests. Agreement with the SNP-based calls on KIR genes ranges from 72%–100% with a mean of 92%; most differences occur in genes KIR2DS2, KIR2DL2, KIR2DS3, and KIR2DL5 where KPI predicts presence and the SNP-based interpretation predicts absence. Overall, the evidence suggests that KPI’s accuracy is 97% or greater for both KIR gene and haplotype-pair predictions, and the presence/absence genotyping leads to ambiguous haplotype-pair predictions with 16 reference KIR haplotype structures. KPI is free, open, and easily executable as a Nextflow workflow supported by a Docker environment at https://github.com/droeatumn/kpi.

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“…These studies have led to the combination of KIR and HLA genotyping in the selection of stem cell donors. Discussion of the selection of unrelated HSCT donors based on HLA and KIR genotyping is outside of the scope of this article but is reviewed by Wright (2020).…”

Section: Kir Content and Transplantationmentioning

confidence: 99%

High-resolution human KIR genotyping

Downing

D’Orsogna

2022

Immunogenetics

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Killer immunoglobulin-like receptors (KIR) regulate the function of natural killer cells through interactions with various ligands on the surface of cells, thereby determining whether natural killer (NK) cells are to be activated or inhibited from killing the cell being interrogated. The genes encoding these proteins display extensive variation through variable gene content, copy number and allele polymorphism. The combination of KIR genes and their ligands is implicated in various clinical settings including haematopoietic stem cell and solid organ transplant and infectious disease progression. The determination of KIR genes has been used as a factor in the selection of optimal stem cell donors with haplotype variations in recipient and donor giving differential clinical outcomes. Methods to determine KIR genes have primarily involved ascertaining the presence or absence of genes in an individual. With the more recent introduction of massively parallel clonal next-generation sequencing and single molecule very long read length third-generation sequencing, high-resolution determination of KIR alleles has become feasible. Determining the extent and functional impact of allele variation has the potential to lead to further optimisation of clinical outcomes as well as a deeper understanding of the functional properties of the receptors and their interactions with ligands. This review summarizes recently published high-resolution KIR genotyping methods and considers the various advantages and disadvantages of the approaches taken. In addition the application of allele level genotyping in the setting of transplantation and infectious disease control is discussed.

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Killer‐cell immunoglobulin‐like receptor assessment algorithms in haemopoietic progenitor cell transplantation: current perspectives and future opportunities

Cited by 6 publications

References 95 publications

KIR in Allogeneic Hematopoietic Stem Cell Transplantation: Need for a Unified Paradigm for Donor Selection

KIR in Allogeneic Hematopoietic Stem Cell Transplantation: Need for a Unified Paradigm for Donor Selection

Accurate and Efficient KIR Gene and Haplotype Inference From Genome Sequencing Reads With Novel K-mer Signatures

High-resolution human KIR genotyping

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