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Histocompatibility and Donor Selection

The conundrum of HLA-DRB1*14:01/*14:54 and HLA-DRB3*02:01/*02:02 mismatches in unrelated hematopoietic SCT

Bone Marrow Transplantation volume 46, pages 916–922 (2011)Cite this article

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Abstract

Uncertainty still exists on the role of polymorphisms outside the HLA-DRB1 binding site or inside the HLA-DRB3 binding groove in unrelated hematopoietic SCT (HSCT). The ideal model to solve the conundrum consists of the transplants mismatched for HLA-DRB1*14:01/*14:54 and/or for HLA-DRB3*02:01/*02:02. A task force was set up in Italy to recruit transplanted pairs defined as HLA-DRB1*14:01 before 2006, the year crucial for the proper definition of the HLA-DRB1*14:54 allele in molecular biology. Out of 2723 unrelated pairs, 189 transplanted in Italy from 1995 to 2006 were HLA-DRB1*14:01 positive; 103/189 pairs with good historical DNA were retyped for HLA-DRB1*14 and HLA-DRB3 at-high resolution level; 31/103 pairs had HLA-DRB1*14 and/or HLA-DRB3 mismatched; 99/103, having complete clinical data, underwent statistical analysis for OS, TRM, disease-free survival and acute and chronic GvHD. No significant involvement of HLA-DRB1*14:01/*14:54 or HLA-DRB3*02:01/*02:02 mismatches was found, either alone or combined. Our findings suggest that disparities at exon 3 of the HLA-DRB1 gene seem unlikely to influence the outcome after HSCT. The same may be envisaged for HLA-DRB3*02:01 and *02:02 alleles which, although differing in the Ag binding site, seem unable to modulate an appreciable immune response in an HSCT setting.

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Acknowledgements

We are grateful to Gruppo Italiano Trapianti Midollo Osseo, who gave us the clinical data of the recipients, to the Italian Bone Marrow Donor Registry, who selected the pairs suitable for the analyses and to the Immunogenetics Italian Laboratories for their precious support throughout the conduct of this study. This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro, the Current Research Projects 2008–2011 and 2009–2010 (Responsible Dr M Martinetti) of the IRCCS Foundation Policlinico San Matteo of Pavia, the Cariplo Foundation and the Telethon Foundation.

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Authors and Affiliations

  1. Immunogenetics Laboratory, Immunohematology and Transfusion Center, IRCCS Foundation, Policlinico San Matteo, Pavia, Italy

    A Pasi & M Martinetti

  2. Department of Health Sciences, Biostatistics Unit, University of Genova, Genova, Italy

    R Crocchiolo

  3. Immunohematology, Hospital Ospedali Riuniti, Bergamo, Italy

    M Bontempelli

  4. Department of Internal Medicine, Medical Genetics, University of Cagliari, Cagliari, Italy

    C Carcassi

  5. Clinical Immunology and Allergology, Hospital Spedali Civili, Brescia, Italy

    G Carella

  6. Department of Regenerative Medicine—Organ and Tissues Transplant Immunology, Foundation IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy

    L Crespiatico

  7. Tissue Typing Laboratory, Hospital Galliera, Genova, Italy

    L Garbarino

  8. Department of Transfusion Medicine, Hospital Riuniti, Trieste, Italy

    L Mascaretti

  9. HLA Tissue Typing, Immunohematology and Transfusion Medicine Service and Cancer Immunotherapy and Gene Therapy Program, IRCCS, Milano, Italy

    B Mazzi & K Fleischhauer

  10. Hospital San Giovanni Battista, Torino, Italy

    G Mazzola

  11. Tissue Typing Laboratory, Hospital S. M. Misericordia, Udine, Italy

    V Miotti

  12. Medical Genetics and Immunogenetics, University Hospital Careggi, Firenze, Italy

    B Porfirio

  13. Immunohematology and Transfusion Center, Medical Genetics, Hospital, Vicenza, Italy

    C Tagliaferri

  14. Tissue Typing Laboratory, Medical Genetics, University ‘La Sapienza’, Hospital San Camillo Forlanini, Rome, Italy

    T Valentini

  15. Immunohematology and Transfusion Center, Hospital, Bolzano, Italy

    C Vecchiato

  16. Division of Regenerative Medicine and Stem Cell Therapy, Unit of Molecular and Functional Immunogenetics, IRCCS San Raffaele, Milano, Italy

    K Fleischhauer

  17. Italian Bone Marrow Donor Registry and Italian Cord Blood Network, Hospital Galliera, Genova, Italy

    N Sacchi

  18. Department of Hematology, University of Florence, Florence, Italy

    A Bosi

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  1. A Pasi
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  2. R Crocchiolo
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  14. T Valentini
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  16. K Fleischhauer
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Correspondence to M Martinetti.

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Pasi, A., Crocchiolo, R., Bontempelli, M. et al. The conundrum of HLA-DRB1*14:01/*14:54 and HLA-DRB3*02:01/*02:02 mismatches in unrelated hematopoietic SCT. Bone Marrow Transplant 46, 916–922 (2011). https://doi.org/10.1038/bmt.2010.246

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  • DOI: https://doi.org/10.1038/bmt.2010.246

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