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Graft-Versus-Host Disease

Combining altered levels of effector transcripts in circulating T cells with a marker of endothelial injury is specific for active graft-versus-host disease

Bone Marrow Transplantation volume 32, pages 1077–1084 (2003)Cite this article

Summary:

Cytotoxic T lymphocytes (CTLs) are important effector cells of graft-versus-host disease (GVHD) and vascular endothelial cells are target cells of allospecific CTL. A combined assessment of T-cell activation and endothelial injury should result in a specific and sensitive test for GVHD. We examined circulating T lymphocytes for effector molecules involved in CTL-mediated endothelial injury. We analyzed CD4 and CD8 T lymphocytes of 24 long-term survivors of allogeneic stem cell transplantation with or without GVHD, and nine healthy, age-matched controls for signs of CTL activation and endothelial injury. IFN-γ transcript levels in CD8 T cells were significantly elevated in SCT recipients with GVHD compared to patients without GVHD (767 CD3ɛ units/T cell (376–2050) vs 211 CD3ɛ units/T cell (159–274), P=0.01). Fas ligand transcript levels in CD4 T cells were significantly elevated in SCT recipients without GVHD compared to patients with GVHD (20 CD3ɛ units/T cell (0–78) vs 0 CD3ɛ units/T cell (0–0), P=0.01). Von Willebrand factor plasma levels were high in patients with GVHD, but normal in patients without GVHD (209 (186–254) vs 120 (100–141), P=0.0005). This assessment of T-cell activation and endothelial injury results in a sensitive and specific test to identify patients with active chronic GVHD.

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Acknowledgements

We thank the medical staff of the Division of Hematology for their support and expert care for the patients included in this study, D Wittwer and I Grilli for excellent technical assistance, J Passweg for critically reading the manuscript and advice on statistical analysis and R Krapf for helpful discussion and support. This study was supported by a grant from the Swiss National Science Foundation (#31-55948), by the Krebsliga Beider, Basel and by the NIH (HL62188).

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Authors and Affiliations

  1. Department of Medicine, University Hospital Bruderholz, Bruderholz, Switzerland

    B C Biedermann

  2. Department of Research, University Hospital Basel, Switzerland

    B C Biedermann

  3. Division of Hematology, University Hospital Basel, Basel, Switzerland

    D A Tsakiris, M Gregor & A Gratwohl

  4. Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT, USA

    J S Pober

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  1. B C Biedermann
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  2. D A Tsakiris
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  3. M Gregor
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  4. J S Pober
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  5. A Gratwohl
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Correspondence to B C Biedermann.

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Biedermann, B., Tsakiris, D., Gregor, M. et al. Combining altered levels of effector transcripts in circulating T cells with a marker of endothelial injury is specific for active graft-versus-host disease. Bone Marrow Transplant 32, 1077–1084 (2003). https://doi.org/10.1038/sj.bmt.1704258

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