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

Kirsten Geneugelijk, Kirsten A. Thus, Hanneke W. M. van Deutekom, Jorg J. A. Calis, Eric Borst, Can Keşmir, Machteld Oudshoorn, Bronno van der Holt, Ellen Meijer, Sacha Zeerleder, Marco R. de Groot, Peter A. von dem Borne, Nicolaas Schaap, Jan Cornelissen, J. rgen Kuball, Eric Spierings

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Abstract

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.
Original languageEnglish
Article number880
Pages (from-to)880
JournalFrontiers in Immunology
Volume10
Issue numberAPR
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

Geneugelijk, K., Thus, K. A., van Deutekom, H. W. M., Calis, J. J. A., Borst, E., Keşmir, C., ... Spierings, E. (2019). Exploratory Study of Predicted Indirectly ReCognizable HLA Epitopes in Mismatched Hematopoietic Cell Transplantations. Frontiers in Immunology, 10(APR), 880. [880]. https://doi.org/10.3389/fimmu.2019.00880