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Graft Versus Host Disease

Increased levels of immune transcript in patients with acute GVHD after allogeneic stem cell transplantation

Bone Marrow Transplantation volume 31, pages 183–190 (2003)Cite this article

Summary:

After allogeneic stem cell transplantation (SCT), donor T-cells are primarily responsible for the antihost activity, resulting in graft-versus-host disease (GVHD). Three effector pathways have been described for T-cell cytotoxicity: perforin/granzyme B; Fas/Fas ligand (FasL) and secreted molecules such as TNF-α. The goal of this pilot study was to utilize competitive reverse transcription (RT)-PCR to evaluate the pattern of granzyme B, perforin, FasL and TNF-α gene expression in peripheral blood in patients after SCT. Protein levels of granzyme B, soluble FasL (sFasL) and TNF-α in plasma were also analyzed. Eight patients who underwent allogeneic SCT were included; five were diagnosed with acute GVHD. In the patients diagnosed with acute GVHD, we found increased levels of granzyme B, perforin and FasL mRNA, although this did not correlate with the clinical severity. However, patients with increasing levels of gene expression during acute GVHD treatment may have an increased risk of developing severe acute GVHD, as two out of three patients with increasing immune transcript levels during GVHD therapy developed life-threatening acute GVHD. In conclusion, the quantitative RT-PCR of granzyme B, perforin and FasL may serve as a guide to the clinician in diagnosing acute GVHD and monitoring treatment.

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Acknowledgements

The authors thank Berit Sundberg for excellent technical assistance, as well as the staff at the Center for Allogeneic Stem Cell Transplantation, Department of Hematology and Pediatrics for competent and compassionate patient care. We also thank Olle Ringdén for critical reading of the manuscript. This study was supported from the following grants: the Swedish Cancer Society (0070-B99-13XAC), the Tore Nilsson foundation for medical research, the Children's Cancer Foundation (1997/073, 2001/012), the Swedish Foundation for Medical Research (SSMF) and the Swedish Medical Society (2001-1299) the Cancer Society in Stockholm, the Tobias Foundation, the FRF Foundation and the Karolinska Institute.

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Authors and Affiliations

  1. Division of Clinical Immunology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden

    M Jaksch, M Uzunel, G Martinez Cangana, M Remberger & J Mattsson

  2. Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden

    M Jaksch, M Uzunel, M Remberger & J Mattsson

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  1. M Jaksch
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Jaksch, M., Uzunel, M., Martinez Cangana, G. et al. Increased levels of immune transcript in patients with acute GVHD after allogeneic stem cell transplantation. Bone Marrow Transplant 31, 183–190 (2003). https://doi.org/10.1038/sj.bmt.1703807

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