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Histocompatibility and Donor Selection Issues

Physiochemical disparity of mismatched HLA class I alloantigens and risk of acute GVHD following HSCT

Bone Marrow Transplantation volume 50, pages 540–544 (2015)Cite this article

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Abstract

We determined whether assessment of the immunogenicity of individual donor–recipient HLA mismatches based on differences in their amino-acid sequence and physiochemical properties predicts clinical outcome following haematopoietic SCT (HSCT). We examined patients transplanted with 9/10 single HLA class I-mismatched grafts (n=171) and 10/10 HLA-A-, -B-, -C-, -DRB1- and -DQB1-matched grafts (n=168). A computer algorithm was used to determine the physiochemical disparity (electrostatic mismatch score (EMS) and hydrophobic mismatch score (HMS)) of mismatched HLA class I specificities in the graft-versus-host direction. Patients transplanted with HLA-mismatched grafts with high EMS/HMS had increased incidence of ⩾grade II acute GVHD (aGVHD) compared with patients transplanted with low EMS/HMS grafts; patients transplanted with low and medium EMS/HMS grafts had similar incidence of aGVHD to patients transplanted with 10/10 HLA-matched grafts. Mortality was higher following single HLA-mismatched HSCT but was not correlated with HLA physiochemical disparity. Assessment of donor–recipient HLA incompatibility based on physiochemical HLA disparity may enable better selection of HLA-mismatched donors in HSCT.

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Acknowledgements

VK, CJT and JAB were funded by the NIHR Cambridge Biomedical Research Centre. We thank the staff of the section Immunogenetics and Transplantation Immunology of the Leiden University Medical Centre for HLA typing all donors and patients.

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Authors and Affiliations

  1. Department of Surgery, University of Cambridge, and NIHR Cambridge Biomedical Research Centre, Cambridge, UK

    V Kosmoliaptsis, D H Mallon & J A Bradley

  2. Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, UK

    V Kosmoliaptsis & C J Taylor

  3. Europdonor Foundation, Leiden, The Netherlands

    M M Jöris, M Oudshoorn & J J van Rood

  4. Department of Immunohematology and Blood Transfusion, LUMC, Leiden, The Netherlands

    M M Jöris, M Oudshoorn, J J van Rood & F H J Claas

  5. Department of Pediatrics, LUMC, Leiden, The Netherlands

    A C Lankester

  6. Department of Hematology, LUMC, Leiden, The Netherlands

    P A von dem Borne

  7. Department of Hematology and Immunology, UMCU, Utrecht, The Netherlands

    J Kuball

  8. Wilhelmina Children’s Hospital, UMCU, Utrecht, The Netherlands

    M Bierings

  9. Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands

    J J Cornelissen

  10. HOVON Data Centre, Erasmus MC Cancer Institute-Clinical Trial Center, Rotterdam, The Netherlands

    M E Groenendijk–Sijnke & B van der Holt

Authors
  1. V Kosmoliaptsis
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  2. M M Jöris
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  5. P A von dem Borne
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  6. J Kuball
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  7. M Bierings
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  8. J J Cornelissen
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  10. B van der Holt
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  11. J A Bradley
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  12. M Oudshoorn
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  13. J J van Rood
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  14. C J Taylor
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  15. F H J Claas
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Correspondence to V Kosmoliaptsis.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on Bone Marrow Transplantation website

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Kosmoliaptsis, V., Jöris, M., Mallon, D. et al. Physiochemical disparity of mismatched HLA class I alloantigens and risk of acute GVHD following HSCT. Bone Marrow Transplant 50, 540–544 (2015). https://doi.org/10.1038/bmt.2014.305

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