Computational Analysis of HLA-presentation of Non-synonymous Recipient Mismatches Indicates Effect on the Risk of Chronic Graft-vs.-Host Disease After Allogeneic HSCT
Nihtinen A; Itälä-Remes M; Putkonen M; Niittyvuopio R; Ritari J; Partanen J; Koskela S; Pastinen T; Kwan T; Salmenniemi U; Volin L; Hyvärinen K
Computational Analysis of HLA-presentation of Non-synonymous Recipient Mismatches Indicates Effect on the Risk of Chronic Graft-vs.-Host Disease After Allogeneic HSCT
Nihtinen A
Itälä-Remes M
Putkonen M
Niittyvuopio R
Ritari J
Partanen J
Koskela S
Pastinen T
Kwan T
Salmenniemi U
Volin L
Hyvärinen K
FRONTIERS MEDIA SA
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042713207
https://urn.fi/URN:NBN:fi-fe2021042713207
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]