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Graft-Versus-Host Disease

A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT

Bone Marrow Transplantation volume 46, pages 1455–1463 (2011)Cite this article

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Abstract

IL-17 has an important role in the host defense against extracellular pathogens and the pathophysiology of autoimmune diseases. This study retrospectively examined the impact of a single-nucleotide polymorphism (rs2275913, G197A) in the IL-17 gene of a total 510 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in HLA-matched myeloablative (discovery study) and nonmyeloablative (validation study) BMT through the Japan Marrow Donor Program (JMDP). In the discovery study, the presence of a 197A genotype in the recipient resulted in a higher incidence of grades II–IV acute GVHD (hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.23–2.85; P=0.004). The donor IL-17A genotype did not significantly influence the transplant outcomes. The validation study showed a trend toward an association of the recipient 197A genotype with an increased risk of grades III–IV acute GVHD (HR, 5.84; 95% CI, 0.75–45.72; P=0.09), as well as a significantly increased risk for chronic GVHD (HR, 3.86; 95% CI, 1.29–11.59; P=0.02). These results suggest an association of the 197A genotype in the recipient side with the development of acute GVHD.

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Acknowledgements

We are indebted to Drs Hiroko Oshima, Masanobu Oshima and Atsushi Hirao, Ms Kayoko Yamada, Mayu Yamada and Yuki Motohashi at Kanazawa University, and Dr Keitaro Matsuo at Aichi Cancer Center Research Institute for their technical assistance. We thank all of the Japan Marrow Donor Program transplant teams who have contributed patients and donors to this study. This study was supported by grants from the Ministry of Health, Labor and Welfare, and the Ministry of Education, Culture, sports and Technology, and Funds from the Mitani Research and Development Assistance Organization (Kanazawa, Japan) and by the Japan Leukemia Research Fund (Tokyo, Japan).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Kanazawa University Hospital, Kanazawa, Japan

    J L Espinoza, A Takami, S Ohtake & S Nakao

  2. Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan

    M Onizuka

  3. Division of Epidemiology, Aichi Cancer Center Hospital, Nagoya, Japan

    T Kawase

  4. Department of Hematology, Meitetsu Hospital, Nagoya, Japan

    H Sao

  5. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    H Akiyama

  6. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    K Miyamura

  7. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    S Okamoto

  8. Department of Hematology and Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan

    M Inoue

  9. Hematopoietic Stem Cell Transplantation Unit, National Cancer Center Hospital, Tokyo, Japan

    T Fukuda

  10. Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan

    Y Morishima

  11. Department of Promotion for Blood and Marrow Transplantation, Aichi Medical University, Nagoya, Japan

    Y Kodera

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Espinoza, J., Takami, A., Onizuka, M. et al. A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT. Bone Marrow Transplant 46, 1455–1463 (2011). https://doi.org/10.1038/bmt.2010.325

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