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Association between recipient TNF rs361525 and acute GVHD: results from analysis of BMT CTN-0201 samples

Bone Marrow Transplantation volume 53, pages 1069–1071 (2018)Cite this article

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To the Editor,

Acute graft-versus-host disease (aGVHD) complicates up to half of all allogeneic hematopoietic cell transplants (allo-HCT) [1]. Given our limited progress in the treatment of aGVHD [2], predictive methods that allow for early intervention are desirable. In a recent meta-analysis of 6 studies (627 patients), we demonstrated a borderline association between the A allele of recipient tumor necrosis factor (TNF) single nucleotide polymorphism (SNP) rs361525 and higher risks of grade II-IV aGVHD (risk ratio: 1.29, 95% confidence interval: 0.99–1.69, P = 0.06) [3]. rs361525G > A is an intronic upstream variant (2KB) TNF SNP with a global minor allele frequency of 6%. Our rationale for focusing on this SNP was the following: (i) rs361525G > A is a functional promoter variant associated with reduced TNFα production [4]; (ii) Increased TNFα expression by tissue macrophages and higher serum TNFα levels after conditioning have been associated with severe aGVHD [5,6,7]; (iii) SNPs increasing TNFα production by gut-resident macrophages could potentially increase donor T-cell reactivity and thus the risk of subsequent aGVHD [8]; and (iv) TNFα is uniformly and highly specifically expressed in gut biopsies of patients with aGVHD [9].

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Acknowledgements

Support for the original trial was provided to the Blood and Marrow Transplant Clinical Trials Network by grant #U10HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute. The Department of the Navy, Office of Naval Research, and the National Marrow Donor Program also supported this study. Enrollment support was provided by DKMS Germany. Any views, opinions, findings, conclusions or recommendations expressed in this material are those of the author(s) and do not reflect the views or the official policy or position of the above mentioned parties.

Funding

This study was funded by a University of Minnesota Marrow on the Move Award to Armin Rashidi, and in part by NIH P30 CA77598 utilizing the Biospecimen Repository in the Translational Therapy Laboratory Shared Resource of the Masonic Cancer Center, University of Minnesota.

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  1. These authors contributed equally: Armin Rashidi, Ryan Shanley.

Authors and Affiliations

  1. Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Armin Rashidi, Jeffrey S. Miller & Daniel J. Weisdorf

  2. Masonic Cancer Center Biostatistics Core, University of Minnesota, Minneapolis, MN, USA

    Ryan Shanley

  3. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    Sophia L. Yohe & Bharat Thyagarajan

  4. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Julie Curtsinger

  5. Moffitt Cancer Center, Tampa, FL, USA

    Claudio Anasetti

  6. Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA

    Edmund K. Waller

  7. Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Bruce R. Blazar

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  1. Armin Rashidi
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Correspondence to Armin Rashidi.

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Rashidi, A., Shanley, R., Yohe, S.L. et al. Association between recipient TNF rs361525 and acute GVHD: results from analysis of BMT CTN-0201 samples. Bone Marrow Transplant 53, 1069–1071 (2018). https://doi.org/10.1038/s41409-018-0127-3

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