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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1417-1424. Prepublished online as a Blood First Edition Paper on October 23, 2003; DOI 10.1182/blood-2003-04-1279. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-04-1279v1 103/4/1417    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zino, E. Articles by Fleischhauer, K. Search for Related Content PubMed PubMed Citation Articles by Zino, E. Articles by Fleischhauer, K. Related Collections Immunobiology Transplantation Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation Elisabetta Zino, Guido Frumento, Sarah Marktel, Maria Pia Sormani, Francesca Ficara, Simona Di Terlizzi, Anna Maria Parodi, Ruhena Sergeant, Miryam Martinetti, Andrea Bontadini, Francesca Bonifazi, Daniela Lisini, Benedetta Mazzi, Silvano Rossini, Paolo Servida, Fabio Ciceri, Chiara Bonini, Edoardo Lanino, Giuseppe Bandini, Franco Locatelli, Jane Apperley, Andrea Bacigalupo, Giovanni Battista Ferrara, Claudio Bordignon, and Katharina Fleischhauer From the HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Hematology and Bone Marrow Transplantation Unit, Cancer Immunotherapy and Gene Therapy Program, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Scientifico H. S. Raffaele, Milan, Italy; Immunogenetics Laboratory, Unit of Clinical Epidemiology and Trials, IRCCS National Institute for Cancer Research, Genoa, Italy; Department of Hematology, Imperial College, London, United Kingdom; HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, Department of Pediatric Hematology-Oncology, IRCCS Policlinico S. Matteo, Pavia, Italy; HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, Institute of Hematology and Medical Oncology, University of Bologna, Ospedale S. Orsola-Malpighi, Bologna, Italy; Department of Pediatric Hematology-Oncology, IRCCS G. Gaslini, Genoa, Italy; Department of Hematology, Ospedale San Martino, Genoa, Italy; and Department of Oncology, Biology and Genetics, University of Genoa, Genoa, Italy. The importance of HLA-DPB1 matching for the outcome of allogeneic hematologic stem cell (HSC) transplantation is controversial. We have previously identified HLA-DPB1*0901 as a target of cytotoxic T cells mediating in vivo rejection of an HSC allograft. Here we show that HLA-DPB1*0901 encodes a T-cell epitope shared by a subset of DPB1 alleles that determines nonpermissive mismatches for HSC transplantation. Several T-cell clones obtained from the patient at the time of rejection showed HLA-DP restricted recognition of allogeneic targets expressing HLA-DPB1*0901, *1001, *1701, *0301, *1401, and *4501, but not other alleles. Based on these findings, we developed an algorithm for prediction of nonpermissive HLA-DPB1 mismatches. Retrospective evaluation of 118 transplantations showed that the presence of nonpermissive HLA-DPB1 mismatches was correlated with significantly increased hazards of acute grade II to IV graft-versus-host disease (HR = 1.87, P = .046) and transplantation-related mortality (HR = 2.69, P = .027) but not relapse (HR = 0.98, P = .939), as compared with the permissive group. There was also a marked but statistically not significant increase in the hazards of overall mortality (HR = 1.64, P = .1). These data suggest that biologic characterization of in vivo alloreactivity can be a tool for definition of clinically relevant nonpermissive HLA mismatches for unrelated HSC transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Crocchiolo, E. Zino, L. Vago, R. Oneto, B. Bruno, S. Pollichieni, N. Sacchi, M. P. Sormani, J. Marcon, T. Lamparelli, et al. Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation Blood, August 13, 2009; 114(7): 1437 - 1444. [Abstract] [Full Text] [PDF] L. Vago, B. Forno, M. P. Sormani, R. Crocchiolo, E. Zino, S. Di Terlizzi, M. T. Lupo Stanghellini, B. Mazzi, S. K. Perna, A. Bondanza, et al. Temporal, quantitative, and functional characteristics of single-KIR-positive alloreactive natural killer cell recovery account for impaired graft-versus-leukemia activity after haploidentical hematopoietic stem cell transplantation Blood, October 15, 2008; 112(8): 3488 - 3499. [Abstract] [Full Text] [PDF] B. E. Shaw, T. A. Gooley, M. Malkki, J. A. Madrigal, A. B. Begovich, M. M. Horowitz, A. Gratwohl, O. Ringden, S. G. E. Marsh, and E. W. Petersdorf The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation Blood, December 15, 2007; 110(13): 4560 - 4566. [Abstract] [Full Text] [PDF] T. Kawase, Y. Morishima, K. Matsuo, K. Kashiwase, H. Inoko, H. Saji, S. Kato, T. Juji, Y. Kodera, T. Sasazuki, et al. High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism Blood, October 1, 2007; 110(7): 2235 - 2241. [Abstract] [Full Text] [PDF] K. Fleischhauer, F. Locatelli, M. Zecca, M. G. Orofino, C. Giardini, P. De Stefano, A. Pession, A. M. Iannone, C. Carcassi, E. Zino, et al. Graft rejection after unrelated donor hematopoietic stem cell transplantation for thalassemia is associated with nonpermissive HLA-DPB1 disparity in host-versus-graft direction Blood, April 1, 2006; 107(7): 2984 - 2992. [Abstract] [Full Text] [PDF]

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