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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2235-2241. Prepublished online as a Blood First Edition Paper on June 6, 2007; DOI 10.1182/blood-2007-02-072405. This Article Full Text Full Text (PDF) Supplemental Tables Supplemental Appendix All Versions of this Article: blood-2007-02-072405v1 110/7/2235    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 Kawase, T. Articles by Sasazuki, T. Search for Related Content PubMed PubMed Citation Articles by Kawase, T. Articles by Sasazuki, T. Related Collections Plenary Papers Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPER High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism Takakazu Kawase1, Yasuo Morishima2, Keitaro Matsuo3, Koichi Kashiwase4, Hidetoshi Inoko5, Hiroh Saji6, Shunichi Kato7, Takeo Juji8, Yoshihisa Kodera9, Takehiko Sasazuki10, for The Japan Marrow Donor Program 1 Division of Immunology, Aichi Cancer Center, Nagoya; 2 Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya; 3 Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya; 4 Japanese Red Cross Tokyo Metropolitan Blood Center, Tokyo; 5 Division of Molecular Science, Tokai University School of Medicine, Isehara; 6 Human Leukocyte Antigen (HLA) Laboratory, Nonprofit Organization (NPO), Kyoto; 7 Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara; 8 Japanese Red Cross Central Blood Institute, Tokyo; 9 Japanese Red Cross Nagoya First Hospital, Nagoya; 10 International Medical Center of Japan, Tokyo, Japan In allogenic hematopoietic stem-cell transplantation, an effect of HLA locus mismatch in allele level on clinical outcome has been clarified. However, the effect of each HLA allele mismatch combination is little known, and its molecular mechanism to induce acute graft-versus-host disease (aGVHD) remains to be elucidated. A total of 5210 donor-patient pairs who underwent transplantation through Japan Marrow Donor Program were analyzed. All HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were retrospectively typed in all pairs. The impacts of the HLA allele mismatch combinations and amino acid substitution positions in 6 HLA loci on severe aGVHD were analyzed. A total of 15 significant high-risk HLA allele mismatch combinations and 1 HLA-DRB1-DQB1 linked mismatch combinations (high-risk mismatch) for severe aGVHD were identified, and the number of high-risk mismatches was highly associated with the occurrence of severe aGVHD regardless of the presence of mismatch combinations other than high-risk mismatch. Furthermore, 6 specific amino acid substitution positions in HLA class I were identified as those responsible for severe aGVHD. These findings provide evidence to elucidate the mechanism of aGVHD on the basis of HLA molecule. Furthermore, the identification of high-risk mismatch, that is, nonpermissive mismatch, would be beneficial for the selection of a suitable donor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation Stephanie J. Lee, John Klein, Michael Haagenson, Lee Ann Baxter-Lowe, Dennis L. Confer, Mary Eapen, Marcelo Fernandez-Vina, Neal Flomenberg, Mary Horowitz, Carolyn K. Hurley, Harriet Noreen, Machteld Oudshoorn, Effie Petersdorf, Michelle Setterholm, Stephen Spellman, Daniel Weisdorf, Thomas M. Williams, and Claudio Anasetti Blood 2007 110: 4576-4583. [Abstract] [Full Text] [PDF] This article has been cited by other articles: K. Sugimoto, M. Murata, S. Terakura, and T. Naoe CTL Clones Isolated from an HLA-Cw-Mismatched Bone Marrow Transplant Recipient with Acute Graft-Versus-Host Disease J. Immunol., November 1, 2009; 183(9): 5991 - 5998. [Abstract] [Full Text] [PDF] J. L. Espinoza, A. Takami, M. Onizuka, H. Sao, H. Akiyama, K. Miyamura, S. Okamoto, M. Inoue, Y. Kanda, S. Ohtake, et al. NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies Haematologica, October 1, 2009; 94(10): 1427 - 1434. [Abstract] [Full Text] [PDF] 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] M. Arora, D. J. Weisdorf, S. R. Spellman, M. D. Haagenson, J. P. Klein, C. K. Hurley, G. B. Selby, J. H. Antin, N. A. Kernan, C. Kollman, et al. HLA-Identical Sibling Compared With 8/8 Matched and Mismatched Unrelated Donor Bone Marrow Transplant for Chronic Phase Chronic Myeloid Leukemia J. Clin. Oncol., April 1, 2009; 27(10): 1644 - 1652. [Abstract] [Full Text] [PDF] T. Kawase, K. Matsuo, K. Kashiwase, H. Inoko, H. Saji, S. Ogawa, S. Kato, T. Sasazuki, Y. Kodera, Y. Morishima, et al. HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism Blood, March 19, 2009; 113(12): 2851 - 2858. [Abstract] [Full Text] [PDF] K. Aoyama, M. Koyama, K.-i. Matsuoka, D. Hashimoto, T. Ichinohe, M. Harada, K. Akashi, M. Tanimoto, and T. Teshima Improved outcome of allogeneic bone marrow transplantation due to breastfeeding-induced tolerance to maternal antigens Blood, February 19, 2009; 113(8): 1829 - 1833. [Abstract] [Full Text] [PDF] M. Kamoun, J. H. Holmes, A. K. Israni, J. D. Kearns, V. Teal, W. P. Yang, S. E. Rosas, M. M. Joffe, H. Li, and H. I. Feldman HLA-A amino acid polymorphism and delayed kidney allograft function PNAS, December 2, 2008; 105(48): 18883 - 18888. [Abstract] [Full Text] [PDF] K. Sugimoto, M. Murata, S. Terakura, and T. Naoe Characterization of Cytotoxic T Lymphocyte Clones Isolated from Bone Marrow Transplant Recipient with HLA-Cw-Mismatched Donor Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 1247 - 1247. [Abstract] S. Marino, S. Lin, M. Maiers, M. D Haagenson, S. R Spellman, S. J. Lee, T. Wang, J. Klein, and K. Van Besien Identifying Amino Acid Substitution Positions Associated with Day 100 Survival in Unrelated Donor Stem Cell Transplant Using Random Forest Analysis Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 3012 - 3012. [Abstract]

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