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

MM Joris, AC Lankester, P van den Borne, J Kuball, M Bierings, Jan Cornelissen, Marlies Sijnke, Ronnie van der Holt, JJ van Rood, M Oudshoorn, FHJ Claas

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Abstract

Introduction: Previously we developed a weighted amino acid (AA) mismatch score predictive for cytotoxic T cell (CTL) alloreactivity (in vitro Clip assay) based on the structure of the HLA class I molecule. The aim of this study is to confirm the clinical relevance of the Clip 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 HIA 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. (C) 2014 Elsevier B.V. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)59-64
Number of pages6
JournalTransplant Immunology
Volume30
Issue number2-3
DOIs
Publication statusPublished - 2014

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  • EMC MM-02-41-04

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