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Minor Histocompatibility Antigen Typing by DNA Sequencing for Clinical Practice in Hematopoietic Stem-Cell Transplantation

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Immunogenetics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 882))

Abstract

In HLA-matched stem-cell transplantation (SCT), minor H antigens are key molecules driving allo-immune responses in both graft-versus-host disease (GvHD) and in graft-versus-leukemia (GvL) reactivity. Dissection of the dual function of minor H antigens became evident through their different modes of tissue and cell expression, i.e., hematopoietic system restricted or broad. Broadly expressed minor H antigens are the targets of immune responses in both arms of graft-versus-host (GvH) responses, i.e., both GvHD and GvL, whereas the immune responses against the hematopoietic system-specific minor H antigens are restricted to the GvL arm of SCT. Evidently, it is this latter group of minor H antigens that can function as curative tools for stem-cell (SC)-based immunotherapy of hematological malignancies and disorders. The HLA-matched patient/donor combinations, incompatible for one of the hematopoietic-specific minor H antigens, are suitable for minor H antigen immunotherapy (Goulmy, Immunol Rev 157:125–140, 1997). Information on the minor H antigen phenotype is therefore needed. Hereto, genomic typing for minor H antigens has been implemented in many HLA laboratories. Here, we firstly summarize the relevance of minor H antigens particularly in hematopoietic SCT. Secondly, we describe a method for typing the various polymorphic minor H antigens molecularly identified to date by DNA sequencing.

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Acknowledgments

We thank Talitha de Hoop en Walter van Ginkel, University Medical Center Utrecht, for developing and validating the SBT protocols, Jos Pool and Jos Drabbels, Leiden University Medical Center for developing and validating the uniform PCR-SSP protocols, and Erik Rozemuller, Genome Diagnostics BV, Utrecht, for the implementation of automated allele assignment for minor H antigens after SBT in SBTEngine®.

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Authors and Affiliations

  1. Department of Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands

    Eric Spierings

  2. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

    Els Goulmy

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  1. Eric Spierings
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  2. Els Goulmy
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Correspondence to Els Goulmy .

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Editors and Affiliations

  1. PathWest Laboratory Medicine, Department of Clinical Immunology, Royal Perth Hospital, Wellington Street, Perth, 6000, Australia

    Frank T. Christiansen

  2. Australian Red Cross Blood Service, National Transplant Services, The Royal Melbourne Hospital, 150-154 Batman Street, Melbourne VIC, 3000, Australia

    Brian D. Tait

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Spierings, E., Goulmy, E. (2012). Minor Histocompatibility Antigen Typing by DNA Sequencing for Clinical Practice in Hematopoietic Stem-Cell Transplantation. In: Christiansen, F., Tait, B. (eds) Immunogenetics. Methods in Molecular Biology, vol 882. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-842-9_29

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  • DOI: https://doi.org/10.1007/978-1-61779-842-9_29

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