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
PY - 2019/1/1
Y1 - 2019/1/1
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 HLAEpitopes (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 HLAEpitopes (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 - http://www.scopus.com/inward/record.url?scp=85065756460&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2019.00880
DO - 10.3389/fimmu.2019.00880
M3 - Article
C2 - 31068946
AN - SCOPUS:85065756460
SN - 1664-3224
VL - 10
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 880
ER -