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

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 tr...

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Bibliographic Details
Published in:Frontiers in immunology 2019-04, Vol.10, p.880-880
Main Authors: Geneugelijk, Kirsten, Thus, Kirsten A, van Deutekom, Hanneke W M, Calis, Jorg J A, Borst, Eric, Keşmir, Can, Oudshoorn, Machteld, van der Holt, Bronno, Meijer, Ellen, Zeerleder, Sacha, de Groot, Marco R, von dem Borne, Peter A, Schaap, Nicolaas, Cornelissen, Jan, Kuball, Jürgen, Spierings, Eric
Format: Article
Language:English
Subjects:
HLA
HLA mismatch
HSCT—hematopoietic stem cell transplant
Immunology
Non-permissible mismatch
PIRCHE
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Summary: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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.00880