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Graft Versus Host Disease

Contribution of TNF-α and IL-10 gene polymorphisms to graft-versus-host disease following allo-hematopoietic stem cell transplantation

Abstract

Some cytokines are believed to play a role in the development of acute and chronic GVHD after allo-hematopoietic stem cell transplantation. It has been reported that TNF-α and IL-10 gene polymorphisms are associated with the production of those cytokines and the development of graft failure after organ transplantation and systemic lupus erythematosus. We examined whether TNF-α and IL-10 gene polymorphisms affect the severity of acute GVHD (aGVHD) and chronic GVHD (cGVHD). Sixty-two and 54 patients were available for the analysis of aGVHD and cGVHD, respectively. We analyzed the gene polymorphisms derived from pre- and post-transplant blood cells. Donor-derived TNF2 allele (A) was more frequently detected in patients with aGVHD III/IV than those aGVHD 0-II (2/6 vs 2/56) (P = 0.04). The donors of the patients with cGVHD more frequently possessed a greater number of alleles (allele 13 or more which contain 26 or more CA repeats) in IL-10.G than those without (13/26 vs 5/28) (P = 0.02), and the patients with cGVHD had more CA repeats in donor-derived IL-10.G than those without (mean = 25.2 vs 23.4) (P= 0.01). Donor-derived TNF-308 and IL-10.G alleles may contribute to severe aGVHD and cGVHD, respectively, and will help us distinguish those patients at high risk for GVHD. Bone Marrow Transplantation (2000) 26, 1317–1323.

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References

  1. Ferrara JLM . Paradigm shift for graft-versus-host disease Bone Marrow Transplant 1994 14: 183–184

    CAS  PubMed  Google Scholar 

  2. Antin JH, Ferrara JLM . Cytokine dysregulation and acute graft-versus-host disease Blood 1992 80: 2964–2968

    CAS  PubMed  Google Scholar 

  3. Vogelsang GB, Hess AD . Graft-versus-host disease: new directions for a persistent problem Blood 1994 84: 2061–2067

    CAS  PubMed  Google Scholar 

  4. Vassalli P . The pathophysiology of tumor necrosis factors Annu Rev Immunol 1992 10: 411–452

    Article  CAS  Google Scholar 

  5. Mackay CR, Imhof BA . Cell adhesion in the immune system Immunol Today 1993 14: 99–102

    Article  CAS  Google Scholar 

  6. Holler E, Kolb HJ, Möller A et al. Increased serum levels of tumor necrosis factor α precede major complications of bone marrow transplantation Blood 1990 75: 1011–1016

    CAS  PubMed  Google Scholar 

  7. Hägglund H, Boström L, Remberger M et al. Risk factors for acute graft-versus-host disease in 291 consecutive HLA-identical bone marrow transplant recipients Bone Marrow Transplant 1995 16: 747–753

    PubMed  Google Scholar 

  8. Barak V, Levi-Schaffer F, Nisman B, Nagler A . Cytokine dysregulation in chronic graft-versus-host disease Leuk Lymphoma 1995 17: 169–173

    Article  CAS  Google Scholar 

  9. Remberger M, Ringden O, Markling L . TNFα levels are increased during bone marrow transplantation conditioning in patients who develop acute GVHD Bone Marrow Transplant 1995 15: 99–104

    CAS  PubMed  Google Scholar 

  10. Graze PR, Gale RP . Chronic graft versus host disease: a syndrome of disordered immunity Am J Med 1979 66: 611–620

    Article  CAS  Google Scholar 

  11. Shulman HM, Sullivan KM, Weiden PL et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients Am J Med 1980 69: 204–217

    Article  CAS  Google Scholar 

  12. Rouquette-Gally AM, Boyeldieu D, Gluckman E et al. Autoimmunity in 28 patients after allogeneic bone marrow transplantation: comparison with Sjögren syndrome and scleroderma Br J Haematol 1987 66: 45–47

    Article  CAS  Google Scholar 

  13. Rouquette-Gally AM, Boyeldieu D, Prost AC, Gluckman E . Autoimmunity after allogeneic bone marrow transplantation. A study of 53 long-term-surviving patients Transplantation 1988 46: 238–240

    Article  CAS  Google Scholar 

  14. Llorente L, Richaud-Patin Y, Fior R et al. In vivo production of interleukin-10 by non-T cells in rheumatoid arthritis, Sjögren's syndrome, and systemic lupus erythematosus Arthr Rheum 1994 37: 1647–1655

    Article  CAS  Google Scholar 

  15. Llorente L, Zou W, Levy Y et al. Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus J Exp Med 1995 181: 839–844

    Article  CAS  Google Scholar 

  16. Wilson AG, di Giovine FS, Blakemore AIF, Duff GW . Single base polymorphism in the human tumor necrosis factor alpha (TNFα) gene detectable by NcoI restriction of PCR product Hum Mol Genet 1992 1: 353

    Article  CAS  Google Scholar 

  17. Wilson AG, de Vries N, Pociot F et al. An allelic polymorphism within the human tumor necrosis factor α promoter region is strongly associated with HLA A1, B8, and DR3 alleles J Exp Med 1993 177: 557–560

    Article  CAS  Google Scholar 

  18. Wilson AG, Symons JA, McDowell TL et al. Effect of a polymorphism in the human tumor necrosis factor α promoter on transcriptional activation Proc Natl Acad Sci USA 1997 94: 3195–3199

    Article  CAS  Google Scholar 

  19. Turner DM, Williams DM, Sankaran D et al. An investigation of polymorphism in the interleukin-10 gene promoter Eur J Immunogenet 1997 24: 1–8

    Article  CAS  Google Scholar 

  20. Turner D, Grant SCD, Yonan N et al. Cytokine gene polymorphism and heart transplant rejection Transplantation 1997 64: 776–779

    Article  CAS  Google Scholar 

  21. Eskdale J, Gallagher G . A polymorphic dinucleotide repeat in the human IL-10 promoter Immunogenetics 1995 42: 444–445

    Article  CAS  Google Scholar 

  22. Eskdale J, Wordsworth P, Bowman S et al. Association between polymorphisms at the human IL-10 locus and systemic lupus erythematosus Tissue Antigens 1997 49: 635–639

    Article  CAS  Google Scholar 

  23. Thomas ED, Storb R, Clift RA et al. Bone marrow transplantation New Engl J Med 1975 292: 895–902

    Article  CAS  Google Scholar 

  24. Baker KS, Roncarolo MG, Peters C et al. High spontaneous IL-10 production in unrelated bone marrow transplant recipients is associated with fewer transplant-related complications and early deaths Bone Marrow Transplant 1999 23: 1123–1129

    Article  CAS  Google Scholar 

  25. Middleton PG, Taylor PRA, Jackson G et al. Cytokine gene polymorphisms associated with severe acute graft-versus-host disease in HLA-identical sibling transplants Blood 1998 92: 3943–3948

    CAS  PubMed  Google Scholar 

  26. Morishima Y, Kodera Y, Hirabayashi N et al. Low incidence of acute GVHD in patients transplanted with marrow from HLA-A, B, DR-compatible unrelated donors among Japanese Bone Marrow Transplant 1995 15: 235–239

    CAS  PubMed  Google Scholar 

  27. Morishima Y, Morishita Y, Tanimoto M et al. Low incidence of acute graft-versus-host disease by the administration of methotrexate and cyclosporin in Japanese leukemia patients after bone marrow transplantation from human leukocyte antigen compatible siblings Blood 1989 74: 2252–2256

    CAS  PubMed  Google Scholar 

  28. Nash RA, Pepe MS, Storb R et al. Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate Blood 1992 80: 1838–1845

    CAS  PubMed  Google Scholar 

  29. Beatty PG, Anasetti C, Hansen JA et al. Marrow transplantation from unrelated donors for treatment of hematologic malignancies: effect of mismatching for one HLA locus Blood 1993 81: 249–253

    CAS  PubMed  Google Scholar 

  30. Fiorentino DF, Bond MW, Mosmann TR . Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones J Exp Med 1989 170: 2081–2095

    Article  CAS  Google Scholar 

  31. De Wit D, Van Mechelen M, Zanin C et al. Preferential activation of Th2 cells in chronic graft-versus-host reaction J Immunol 1993 150: 361–366

    CAS  PubMed  Google Scholar 

  32. Körholz D, Kunst D, Hempel L et al. Decreased interleukin 10 and increased interferon-γ production in patients with chronic graft-versus-host disease after allogeneic bone marrow transplantation Bone Marrow Transplant 1997 19: 691–695

    Article  Google Scholar 

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The authors thank Mrs M Sakaue for technical assistance.

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Takahashi, H., Furukawa, T., Hashimoto, S. et al. Contribution of TNF-α and IL-10 gene polymorphisms to graft-versus-host disease following allo-hematopoietic stem cell transplantation. Bone Marrow Transplant 26, 1317–1323 (2000). https://doi.org/10.1038/sj.bmt.1702724

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