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Geneugelijk, K.; Thus, K.A.; Deutekom, H.W.M. van; Calis, J.J.A.; Borst, E.; Kesmir, C.; ... ; Spierings, E. (2019)

Exploratory Study of Predicted Indirectly ReCognizable HLA Epitopes in Mismatched Hematopoietic Cell Transplantations

Article / Letter to editor
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...Show moreHLA-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.Show less
HLA
PIRCHE
Non-permissible mismatch
HSCT-hematopoietic stem cell transplant
HLA mismatch
All authors
Geneugelijk, K.; Thus, K.A.; Deutekom, H.W.M. van; Calis, J.J.A.; Borst, E.; Kesmir, C.; Oudshoorn, M.; Holt, B. van der; Meijer, E.; Zeerleder, S.; Groote, M.R. de; Borne, P.A. von dem; Schaap, N.; Cornelissen, J.; Kuball, J.; Spierings, E.
Date
2019-04-24
Journal
Frontiers in Immunology
Volume
10
DOI
doi:10.3389/fimmu.2019.00880