Loss of endothelial thrombomodulin predicts response to steroid therapy and survival in acute intestinal graft-versus-host disease |
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| Authors: | Mindaugas Andrulis 1 Sascha Dietrich Thomas Longerich Ronald Koschny Maria Burian Annette Schmitt-Gr?f Peter Schirmacher Anthony D. Ho Peter Dreger Thomas Luft |
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| Affiliation: | 1Institute of Pathology, University Hospital Heidelberg;2Unit Adaptive Immune Regulation, German Cancer Research Center;3Department of Medicine V, University of Heidelberg;4Department of Medicine IV, University of Heidelberg;5Interdiscplinary Endoscopy Center, University of Heidelberg;6Institute of Pathology, Freiburg, Germany |
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| Abstract: | Steroid-refractory graft-versus-host disease causes significant morbidity and mortality after allogeneic stem cell transplantation. The pathomechanism of steroid resistance is currently not understood, but it has been suggested that endothelial cell dysfunction plays a role. Endothelial thrombomodulin was quantified along with histological markers of epithelial damage and cytotoxic T cells in colon biopsies from 51 allografted patients, and retrospectively correlated with response to steroids and survival. Loss of endothelial thrombomodulin was the strongest predictor of response to steroids (P=0.02) and nonrelapse mortality (P=0.01) in multivariate analyses adjusting for T-cell infiltrates, histological grading, vessel density, disease status, donor type, and conditioning therapy. Our data provide evidence that at disease onset, loss of endothelial thrombomodulin expression rather than excessive T-cell infiltration associates with steroid-refractory graft-versus-host disease and mortality. Prospective histological investigations are now warranted to improve diagnosis and prognostication of this core complication of stem cell transplantation.Key words: allogeneic stem cell transplantation, acute GvHD, thrombomodulin, endothelial cells, steroid-resistance, cytotoxic T cells, TIA-1 |
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