TY - JOUR
T1 - An Approach to Predicting Hematopoietic Stem Cell Transplantation Outcome Using HLA-Mismatch Information Mapped on Protein Structure Data
AU - Dudkiewicz, Małgorzata
AU - Malanowski, Piotr
AU - Czerwiński, Jarosław
AU - Pawłowski, Krzysztof
N1 - Funding Information:
Financial disclosure: This work was supported by Polish Ministry of Science Grant NN301 2385333. We are grateful to the Central Bone Marrow Donor and CB Registry Poltransplant; Department of Hematology–BMT Unit, Medical University of Gdansk; Department of Hematology and BMT, Medical University of Silesia; Children's University Hospital Hematology–Oncology Lublin, Department of Pediatric Oncology, Hematology & HSCT, Poznan University of Medical Sciences; Department of Hematology, Institute of Haematology and Blood Transfusion, Central Clinical Hospital; Department of Hematology & Oncology, Medical University of Warsaw; the Lower Silesian Center for Cellular Transplantation with the National Bone Marrow Donor Registry; and the Department of Children's Hematology and Oncology, Wroclaw Medical University for their disclosure of post-HSCT data.
PY - 2009/9
Y1 - 2009/9
N2 - 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.
AB - 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.
KW - Conformational search
KW - Donor-recipient matching
KW - HLA mismatch
KW - HLAp-T cell receptor complex
KW - Hematopoietic stem cell transplantation
KW - Protein structure analysis
UR - http://www.scopus.com/inward/record.url?scp=67849133677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67849133677&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2009.05.011
DO - 10.1016/j.bbmt.2009.05.011
M3 - Article
C2 - 19660714
AN - SCOPUS:67849133677
SN - 1083-8791
VL - 15
SP - 1014
EP - 1025
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 9
ER -