Document Type
Article
Publication Date
7-16-2019
Identifier
DOI: 10.3389/fimmu.2019.01625; PMCID: PMC6646417
Abstract
Genetic mismatches in protein coding genes between allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipient and donor can elicit an alloimmunity response via peptides presented by the recipient HLA receptors as minor histocompatibility antigens (mHAs). While the impact of individual mHAs on allo-HSCT outcome such as graft-vs.-host and graft-vs.-leukemia effects has been demonstrated, it is likely that established mHAs constitute only a small fraction of all immunogenic non-synonymous variants. In the present study, we have analyzed the genetic mismatching in 157 exome-sequenced sibling allo-HSCT pairs to evaluate the significance of polymorphic HLA class I associated peptides on clinical outcome. We applied computational mismatch estimation approaches based on experimentally verified HLA ligands available in public repositories, published mHAs, and predicted HLA-peptide affinites, and analyzed their associations with chronic graft-vs.-host disease (cGvHD) grades. We found that higher estimated recipient mismatching consistently increased the risk of severe cGvHD, suggesting that HLA-presented mismatching influences the likelihood of long-term complications in the patient. Furthermore, computational approaches focusing on estimation of HLA-presentation instead of all non-synonymous mismatches indiscriminately may be beneficial for analysis sensitivity and could help identify novel mHAs.
Journal Title
Front Immunol
Volume
10
First Page
1625
Last Page
1625
MeSH Keywords
Genotype; Graft vs Host Disease; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation; Histocompatibility; Histocompatibility Testing; Humans; Minor Histocompatibility Antigens; Siblings; Tissue Donors; Transplantation, Homologous
Keywords
HLA; HSCT; genomics; graft-vs.-host; minor histocompatibility antigen; whole-exome sequencing
Recommended Citation
Ritari J, Hyvärinen K, Koskela S, et al. Computational Analysis of HLA-presentation of Non-synonymous Recipient Mismatches Indicates Effect on the Risk of Chronic Graft-vs.-Host Disease After Allogeneic HSCT. Front Immunol. 2019;10:1625. Published 2019 Jul 16. doi:10.3389/fimmu.2019.01625
Comments
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Publisher's Online Access: https://doi.org/10.3389/fimmu.2019.01625