An Approach to Predicting Hematopoietic Stem Cell Transplantation Outcome Using HLA-Mismatch Information Mapped on Protein Structure Data

Małgorzata Dudkiewicz, Piotr Malanowski, Jarosław Czerwiński, Krzysztof Pawłowski

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

In hematopoietic stem cell transplantation (HSCT), the outcome is predicted using HLA-matching procedures, which are very time-consuming. There exists substantial evidence of the importance of early donor acceptance in HSCT outcome. In cases when the donor cannot be perfectly matched, it often is unclear which mismatch is less harmful and thus has a greater likelihood of acceptance. We modeled and analyzed interactions between the protein products of different HLA alleles of the transplant recipient and natural killer and T lymphocyte cell receptors of the donor's immune system. Reactions between these 2 systems often lead to graft-versus-host disease (GVHD). Sequence polymorphisms that define HLA I and II alleles predict not only GVHD, but also host-versus-graft and graft-versus-leukemia effects, all of which influence the overall transplantation outcome. Although complete high-resolution HLA matching of the donor-recipient pair seems to be associated with optimal post-HSCT survival, recent reports suggest that not every HLA disparity is functionally relevant. We performed interaction energy calculations for selected pairs of donor-recipient HLA alleles. Based on the results, we conclude that the energy of contact between the T lymphocyte cell receptor (TCR) and HLA residues can help predict the future development of an immune reaction and, consequently, the outcome of allogeneic HSCT.

Original languageEnglish (US)
Pages (from-to)1014-1025
Number of pages12
JournalBiology of Blood and Marrow Transplantation
Volume15
Issue number9
DOIs
StatePublished - Sep 2009
Externally publishedYes

Keywords

  • Conformational search
  • Donor-recipient matching
  • Hematopoietic stem cell transplantation
  • HLA mismatch
  • HLAp-T cell receptor complex
  • Protein structure analysis

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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