TY - JOUR
T1 - Exploratory Study of Predicted Indirectly ReCognizable HLA Epitopes in Mismatched Hematopoietic Cell Transplantations
AU - Geneugelijk, Kirsten
AU - Thus, Kirsten A
AU - van Deutekom, Hanneke W M
AU - Calis, Jorg J A
AU - Borst, Eric
AU - Keşmir, Can
AU - Oudshoorn, Machteld
AU - van der Holt, Bronno
AU - Meijer, Ellen
AU - Zeerleder, Sacha
AU - de Groot, Marco R
AU - von dem Borne, Peter A
AU - Schaap, Nicolaas
AU - Cornelissen, Jan
AU - Kuball, Jürgen
AU - Spierings, Eric
N1 - Funding Information:
We further acknowledge support from our funding agency: The KWF grant (UU 2015-7601) to JK and ES, The Netherlands Organization for Scientific Research, Computational Life Sciences Program (grant number 635.100.025) to JC, and NWO Aard en Levenswetenschappen grant (823.02.014) to CK.
Publisher Copyright:
Copyright © 2019 Geneugelijk, Thus, van Deutekom, Calis, Borst, Keşmir, Oudshoorn, van der Holt, Meijer, Zeerleder, de Groot, von dem Borne, Schaap, Cornelissen, Kuball and Spierings.
PY - 2019/4/24
Y1 - 2019/4/24
N2 - HLA-mismatches in hematopoietic stem-cell transplantation are associated with an impaired overall survival (OS). The aim of this study is to explore whether the Predicted Indirectly ReCognizable HLA-Epitopes (PIRCHE) algorithm can be used to identify HLA-mismatches that are related to an impaired transplant outcome. PIRCHE are computationally predicted peptides derived from the patient's mismatched-HLA molecules that can be presented by donor-patient shared HLA. We retrospectively scored PIRCHE numbers either presented on HLA class-I (PIRCHE-I) or class-II (PIRCHE-II) for a Dutch multicenter cohort of 103 patients who received a single HLA-mismatched (9/10) unrelated donor transplant in an early phase of their disease. These patients were divided into low and high PIRCHE-I and PIRCHE-II groups, based on their PIRCHE scores, and compared using multivariate statistical analysis methods. The high PIRCHE-II group had a significantly impaired OS compared to the low PIRCHE-II group and the 10/10 reference group (HR: 1.86, 95%-CI: 1.02-3.40; and HR: 2.65, 95%-CI: 1.53-4.60, respectively). Overall, PIRCHE-II seem to have a more prominent effect on OS than PIRCHE-I. This impaired OS is probably due to an increased risk for severe acute graft-vs.-host disease. These data suggest that high PIRCHE-II scores may be used to identify non-permissible HLA mismatches within single HLA-mismatched hematopoietic stem-cell transplantations.
AB - HLA-mismatches in hematopoietic stem-cell transplantation are associated with an impaired overall survival (OS). The aim of this study is to explore whether the Predicted Indirectly ReCognizable HLA-Epitopes (PIRCHE) algorithm can be used to identify HLA-mismatches that are related to an impaired transplant outcome. PIRCHE are computationally predicted peptides derived from the patient's mismatched-HLA molecules that can be presented by donor-patient shared HLA. We retrospectively scored PIRCHE numbers either presented on HLA class-I (PIRCHE-I) or class-II (PIRCHE-II) for a Dutch multicenter cohort of 103 patients who received a single HLA-mismatched (9/10) unrelated donor transplant in an early phase of their disease. These patients were divided into low and high PIRCHE-I and PIRCHE-II groups, based on their PIRCHE scores, and compared using multivariate statistical analysis methods. The high PIRCHE-II group had a significantly impaired OS compared to the low PIRCHE-II group and the 10/10 reference group (HR: 1.86, 95%-CI: 1.02-3.40; and HR: 2.65, 95%-CI: 1.53-4.60, respectively). Overall, PIRCHE-II seem to have a more prominent effect on OS than PIRCHE-I. This impaired OS is probably due to an increased risk for severe acute graft-vs.-host disease. These data suggest that high PIRCHE-II scores may be used to identify non-permissible HLA mismatches within single HLA-mismatched hematopoietic stem-cell transplantations.
KW - HLA
KW - HLA mismatch
KW - HSCT-hematopoietic stem cell transplant
KW - Non-permissible mismatch
KW - PIRCHE
UR - https://www.scopus.com/pages/publications/85065756460
U2 - 10.3389/fimmu.2019.00880
DO - 10.3389/fimmu.2019.00880
M3 - Article
C2 - 31068946
SN - 1664-3224
VL - 10
SP - 1
EP - 8
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 880
ER -