Translating in vitro prediction of cytotoxic T cell alloreactivity to hematopoietic stem cell transplantation outcome.

Autor: Jöris MM; Europdonor Foundation, The Netherlands; Department of Immunohematology and Blood transfusion, LUMC, The Netherlands. Electronic address: joris@europdonor.nl., Lankester AC; Department of Pediatrics, LUMC, The Netherlands., von dem Borne PA; Department of Hematology, LUMC, The Netherlands., Kuball J; Department of Hematology and Immunology, UMCU, The Netherlands., Bierings M; Wilhelmina Children's Hospital, UMCU, The Netherlands., Cornelissen JJ; Department of Hematology, Erasmus MC-Daniel den Hoed, The Netherlands., Sijnke ME; HOVON Data Center, Erasmus MC-Daniel den Hoed, The Netherlands., van der Holt B; HOVON Data Center, Erasmus MC-Daniel den Hoed, The Netherlands., van Rood JJ; Europdonor Foundation, The Netherlands; Department of Immunohematology and Blood transfusion, LUMC, The Netherlands., Oudshoorn M; Europdonor Foundation, The Netherlands; Department of Immunohematology and Blood transfusion, LUMC, The Netherlands., Claas FH; Department of Immunohematology and Blood transfusion, LUMC, The Netherlands.
Jazyk: angličtina
Zdroj: Transplant immunology [Transpl Immunol] 2014 Mar; Vol. 30 (2-3), pp. 59-64. Date of Electronic Publication: 2014 Jan 17.
DOI: 10.1016/j.trim.2013.08.006
Abstrakt: Introduction: Previously we developed a weighted amino acid (AA) mismatch score predictive for cytotoxic T cell (CTL) alloreactivity (in vitro CTLp assay) based on the structure of the HLA class I molecule. The aim of this study is to confirm the clinical relevance of the CTLp assay and to validate the AA mismatch score as an alternative and easy to use tool to predict permissible mismatches in hematopoietic stem cell transplantation (HSCT).
Methods: We selected patients transplanted with a 9/10 single HLA class I mismatched graft (n=171) at three Dutch HSCT centers. A CTLp assay was performed in 73 donor-recipient pairs. As a control we selected 168 10/10 HLA matched pairs that were matched to the 9/10 single HLA class I mismatched pairs for HSCT year, donor type, patient age and diagnosis.
Results: We observed that pairs with negative a CTLp assay had statistically significant decreased incidence of mortality after HSCT comparable to that of 10/10 HLA matched pairs. However, the weighted AA mismatch score did not significantly predict any HSCT end point of interest.
Conclusion: Further investigation is needed to unravel the mechanisms involved in causing the beneficial effect of a negative CTLp assay, before other alternative tools to predict HSCT outcome may be developed.
(Copyright © 2014 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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