Abstract
The aim of this study was to determine whether the gene polymorphisms of Th1/Th2 and immunoregulatory cytokines were associated with aGVHD in Japanese children receiving allogeneic bone marrow transplantation (allo BMT). We investigated polymorphisms of genes encoding interleukin (IL)-4, IL-4 receptor (IL-4 R), IL-10, transforming growth factor (TGF)-β1, TGF-β1 type II receptor (TGF-β1 RII), interferon (IFN)-γ, IFN-γ type 2 receptor (IFN-γ R2), and IFN regulatory factor (IRF)-1. Sixty-seven patients were treated with alloBMT from HLA-identical siblings, and aGVHD was observed in 38. TGF-β1 codon 10 leucine (Leu) /proline (Pro) polymorphism in donors was associated with the development of aGVHD. Patients having donors with the Pro allele had aGVHD more frequently than those without Pro allele (30/45 vs 8/20, odds ratio = 3.00; P = 0.04). TGF-β1 RII 1167 C/T polymorphism in recipients was also associated with the development of aGVHD. The incidence was significantly higher in recipients with T allele than in those without T allele (21/27 vs 16/35, odds ratio = 4.16; P = 0.01). In conclusion, genetic backgrounds of TGF-β1 and TGF-β1 RII may be involved in the development of aGVHD in HLA-matched sibling BMT in Japanese children.
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References
Rocha V, Wagner JE Jr, Sobocinski KA et al. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources New Engl J Med 2000 342: 1846 1854
Xun CQ, Thompson JS, Jennings CD et al. Effect of total body irradiation, busulfan-cyclophosphamide, or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2- incompatible transplanted SCID mice Blood 1994 83: 2360 2367
Chen Y, Kuchroo VK, Inobe J et al. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis Science 1994 265: 1237 1240
Krenger W, Hill GR, Ferrara JL . Cytokine cascades in acute graft-versus-host disease Transplantation 1997 64: 553 558
Tanaka J, Imamura M, Kasai M et al. The important balance between cytokines derived from type 1 and type 2 helper T cells in the control of graft-versus-host disease Bone Marrow Transplant 1997 19: 571 576
Ellison CA, Fischer JM, HayGlass KT, Gartner JG . Murine graft-versus-host disease in an F1-hybrid model using IFN-gamma gene knockout donors J Immunol 1998 161: 631 640
Hill GR, Cooke KR, Teshima T et al. Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation J Clin Invest 1998 102: 115 123
Yang YG, Dey BR, Sergio JJ et al. Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12 J Clin Invest 1998 102: 2126 2135
Murphy WJ, Welniak LA, Taub DD et al. Differential effects of the absence of interferon-gamma and IL-4 in acute graft-versus-host disease after allogeneic bone marrow transplantation in mice J Clin Invest 1998 102: 1742 1748
Cavet J, Middleton PG, Segall M et al. Recipient tumor necrosis factor-alpha and interleukin-10 gene polymorphisms associate with early mortality and acute graft-versus-host disease severity in HLA-matched sibling bone marrow transplants Blood 1999 94: 3941 3946
Cavet J, Dickinson AM, Norden J et al. Interferon-gamma and interleukin-6 gene polymorphisms associate with graft-versus-host disease in HLA-matched sibling bone marrow transplantation Blood 2001 98: 1594 1600
Cullup H, Dickinson AM, Jackson GH et al. Donor interleukin 1 receptor antagonist genotype associated with acute graft-versus-host disease in human leucocyte antigen-matched sibling allogeneic transplants Br J Haematol 2001 113: 807 813
Middleton PG, Taylor PR, Jackson G et al. Cytokine gene polymorphisms associating with severe acute graft-versus-host disease in HLA-identical sibling transplants Blood 1998 92: 3943 3948
Nakao F, Ihara K, Kusuhara K et al. Association of IFN-gamma and IFN regulatory factor 1 gene polymorphisms with childhood atopic asthma J Allergy Clin Immunol 2001 107: 499 504
Takabayashi A, Ihara K, Sasaki Y et al. Childhood atopic asthma: positive association with a polymorphism of IL-4 receptor alpha gene but not with that of IL-4 promoter or Fc epsilon receptor I beta gene Exp Clin Immunogenet 2000 17: 63 70
Ueno M, Kira R, Matsushima T et al. Moyamoya disease and transforming growth factor-beta1 J Neurosurg 2000 92: 907 908
Przepiorka D, Weisdorf D, Martin P et al. 1994 Consensus Conference on Acute GVHD Grading Bone Marrow Transplant 1995 15: 825 828
Maeda H, Shiraishi A . TGF-beta contributes to the shift toward Th2-type responses through direct and IL-10-mediated pathways in tumor-bearing mice J Immunol 1996 156: 73 78
Zeller JC, Panoskaltsis-Mortari A, Murphy WJ et al. Induction of CD4+ T cell alloantigen-specific hyporesponsiveness by IL-10 and TGF-beta J Immunol 1999 163: 3684 3691
Imamura M, Tanaka J, Hashino S et al. Immunopathogenesis of GVHD Transplant Proc 1996 28: 1181 1183
Liem LM, Fibbe WE, van Houwelingen HC, Goulmy E . Serum transforming growth factor-beta1 levels in bone marrow transplant recipients correlate with blood cell counts and chronic graft-versus-host disease Transplantation 1999 67: 59 65
Holweg CT, Baan CC, Balk AH et al. The transforming growth factor-beta1 codon 10 gene polymorphism and accelerated graft vascular disease after clinical heart transplantation Transplantation 2001 71: 1463 1467
Awad MR, El-Gamel A, Hasleton P et al. Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation Transplantation 1998 66: 1014 1020
Yokota M, Ichihara S, Lin TL et al. Association of a T29→C polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to myocardial infarction in Japanese Circulation 2000 101: 2783 2787
Yamada Y, Hosoi T, Makimoto F et al. Transforming growth factor beta-1 gene polymorphism and bone mineral density in Japanese adolescents Am J Med 1999 106: 477 479
Garcia-Gonzalez MA, Crusius JB, Strunk MH et al. TGFB1 gene polymorphisms and inflammatory bowel disease Immunogenetics 2000 51: 869 872
Garrigue-Antar L, Munoz-Antonia T, Antonia SJ et al. Missense mutations of the transforming growth factor beta type II receptor in human head and neck squamous carcinoma cells Cancer Res 1995 55: 3982 3987
Shin KH, Park YJ, Park JG . Mutational analysis of the transforming growth factor beta receptor type II gene in hereditary nonpolyposis colorectal cancer and early-onset colorectal cancer patients Clin Cancer Res 2000 6: 536 540
Lim S, Crawley E, Woo P, Barnes PJ . Haplotype associated with low interleukin-10 production in patients with severe asthma Lancet 1998 352: 113
Awad M, Pravica V, Perrey C et al. CA repeat allele polymorphism in the first intron of the human interferon-gamma gene is associated with lung allograft fibrosis Hum Immunol 1999 60: 343 346
Pravica V, Asderakis A, Perrey C et al. In vitro production of IFN-gamma correlates with CA repeat polymorphism in the human IFN-gamma gene Eur J Immunogenet 1999 26: 1 3
Chipeta J, Komada Y, Zhang XL et al. CD4+ and CD8+ cell cytokine profiles in neonates, older children, and adults: increasing T helper type 1 and T cytotoxic type 1 cell populations with age Cell Immunol 1998 183: 149 156
Morishima Y, Morishita Y, Tanimoto M et al. Low incidence of acute graft-versus-host disease by the administration of methotrexate and cyclosporine in Japanese leukemia patients after bone marrow transplantation from human leukocyte antigen compatible siblings; possible role of genetic homogeneity. The Nagoya Bone Marrow Transplantation Group Blood 1989 74: 2252 2256
Takahashi K, Juji T, Miyazaki H . Determination of an appropriate size of unrelated donor pool to be registered for HLA-matched bone marrow transplantation Transfusion 1989 29: 311 316
Acknowledgements
We thank Naoko Kinukawa, PhD, the Department of Medical Informatics, Graduate School of Medical Sciences, Kyushu University, for the valuable advice on the statistical analysis, and Ms Tamami Tanaka and Ms Yoko Katafuchi for their excellent technical assistance.
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Hattori, H., Matsuzaki, A., Suminoe, A. et al. Polymorphisms of transforming growth factor-β1 and transforming growth factor-β1 type II receptor genes are associated with acute graft-versus-host disease in children with HLA-matched sibling bone marrow transplantation. Bone Marrow Transplant 30, 665–671 (2002). https://doi.org/10.1038/sj.bmt.1703684
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DOI: https://doi.org/10.1038/sj.bmt.1703684
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