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Cytokines

Polymorphisms in TNFA and TNFR2 affect outcome of unrelated bone marrow transplantation

Bone Marrow Transplantation volume 29, pages 569–575 (2002)Cite this article

Abstract

Effects of polymorphisms in TNFA and TNFR2 on the outcome of 462 cases of unrelated bone marrow transplantation (uBMT) were studied retrospectively. Four alleles of TNFA (U01–U04) distinguished by polymorphism in the upstream region, −1031 (T/C), −863 (C/A) and −857 (C/T), and two alleles of TNFR2 (196M/196R) distinguished by polymorphism at codon 196 were determined. Transplantation involving TNFA-U02- and/or U03-positive donors and/or recipients resulted in a higher incidence of graft-versus-host disease (GVHD) of grade III–IV (P < 0.05 for donor type, P < 0.01 for recipient type) and a lower relapse rate than that involving TNFA-U01 homozygous recipients and/or donors (P < 0.025 for donor type, P < 0.01 for recipient type). These results include the HLA mismatching effect due to linkage disequilibirium of TNFA with HLA loci. However, the effects were also observed in HLA-A, -B and -DRB1 allele-matched transplantation. Transplantation from TNFR2–196R-positive donors exhibited a higher incidence of severe GVHD (P < 0.05) and tendency for a lower relapse rate than that from TNFR2–196M homozygous donors. TNFR2–196R of recipient origin had no effect on GVHD but increased the relapse rate (P < 0.025). These results suggest that TNFA and TNFR2 typings are helpful for predicting uBMT outcome and for preventing severe complications at an early stage.

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Acknowledgements

This work was supported in part by a research fund for Allergy and Organ Transplantation from the Ministry of Health and Welfare of Japan.

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Authors and Affiliations

  1. Japanese Red Cross Central Blood Center, Tokyo, Japan

    Y Ishikawa, K Kashiwase, T Akaza & T Juji

  2. Aichi Cancer Center, Nagoya, Japan

    Y Morishima

  3. The Department of Genetic Information, Division of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan

    H Inoko

  4. The Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    T Sasazuki

  5. The Department of Internal Medicine, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Y Kodera

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Ishikawa, Y., Kashiwase, K., Akaza, T. et al. Polymorphisms in TNFA and TNFR2 affect outcome of unrelated bone marrow transplantation. Bone Marrow Transplant 29, 569–575 (2002). https://doi.org/10.1038/sj.bmt.1703409

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  • DOI: https://doi.org/10.1038/sj.bmt.1703409

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