Comparison of NK alloreactivity prediction models based on KIR-MHC interactions in haematopoietic stem cell transplantation

Frontiers in Immunology

Immunology

Arnaud Campidelli¹  James Traherne²  Vitalina Chamberlain-Evans²  Neda Nemat-Gorgani²  John Trowsdale²  Thomas Remen³  Michaël Pérès⁴  Sandra Clément⁴  Alice Aarnink⁵  Adèle Dhuyser⁵  Marie Thérèse Rubio⁶ 

[1] Department of Hematology, Centre Hospitalier Régional Universitaire de Nancy, Nancy, France;Department of Pathology, University of Cambridge, Cambridge, United Kingdom;Direction de la Recherche Clinique et de l’Innovation, Unité de Méthodologie, Datamanagement et Statistiques, Centre Hospitalier Régional Universitaire de Nancy, Nancy, France;Histocompatibility Laboratory, Centre Hospitalier Régional Universitaire de Nancy, Nancy, France;Histocompatibility Laboratory, Centre Hospitalier Régional Universitaire de Nancy, Nancy, France;Ingénieurie Moléculaire et Physiopathologie Articulaire, team 6 (IMoPA6), Unité Mixte de Recherche 7365 Centre national de la Recherche Scientifique, Université de Lorraine, Nancy, France;Ingénieurie Moléculaire et Physiopathologie Articulaire, team 6 (IMoPA6), Unité Mixte de Recherche 7365 Centre national de la Recherche Scientifique, Université de Lorraine, Nancy, France;Department of Hematology, Centre Hospitalier Régional Universitaire de Nancy, Nancy, France;

关键词: KIR;    MHC;    HLA;    alloreactivity;    prediction;    natural killer (NK);    allogeneic stem cell transplantation;    donor selection;   

DOI  :  10.3389/fimmu.2023.1028162

 received in 2022-08-25, accepted in 2023-01-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

The biological processes underlying NK cell alloreactivity in haematopoietic stem cell transplantation (HSCT) remain unclear. Many different models to predict NK alloreactivity through KIR and MHC genotyping exist, raising ambiguities in its utility and application for clinicians. We assessed 27 predictive models, broadly divided into six categories of alloreactivity prediction: ligand-ligand, receptor-ligand, educational, KIR haplotype-based, KIR matching and KIR allelic polymorphism. The models were applied to 78 NGS-typed donor/recipient pairs undergoing allogeneic HSCT in genoidentical (n=43) or haploidentical (n=35) matchings. Correlations between different predictive models differed widely, suggesting that the choice of the model in predicting NK alloreactivity matters. For example, two broadly used models, educational and receptor-ligand, led to opposing predictions especially in the genoidentical cohort. Correlations also depended on the matching fashion, suggesting that this parameter should also be taken into account in the choice of the scoring strategy. The number of centromeric B-motifs was the only model strongly correlated with the incidence of acute graft-versus-host disease in our set of patients in both the genoidentical and the haploidentical cohorts, suggesting that KIR-based alloreactivity, not MHC mismatches, are responsible for it. To our best knowledge, this paper is the first to experimentally compare NK alloreactivity prediction models within a cohort of genoidentical and haploidentical donor-recipient pairs. This study helps to resolve current discrepancies in KIR-based alloreactivity predictions and highlights the need for deeper consideration of the models used in clinical studies as well as in medical practice.

【 授权许可】

Unknown   
Copyright © 2023 Dhuyser, Remen, Pérès, Chamberlain-Evans, Nemat-Gorgani, Campidelli, Clément, Rubio, Trowsdale, Aarnink and Traherne