Steroid-refractory GVHD: T-cell attack within a vulnerable endothelial system
Acute graft-versus-host disease (GVHD) is a major complication of allogeneic stem cell transplantation (SCT) and can be readily controlled by systemic high-dose steroids in many patients. However, patients whose GVHD is refractory to this therapy have a poor prognosis. Refractory patients have ongoi...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2011
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| In: |
Blood
Year: 2011, Volume: 118, Issue: 6, Pages: 1685-1692 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2011-02-334821 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2011-02-334821 Verlag, lizenzpflichtig, Volltext: https://ashpublications.org/blood/article/118/6/1685/29155/Steroid-refractory-GVHD-T-cell-attack-within-a 
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| Author Notes: | Thomas Luft, Sascha Dietrich, Christine Falk, Michael Conzelmann, Michael Hess, Axel Benner, Frank Neumann, Berend Isermann, Ute Hegenbart, Anthony D. Ho, and Peter Dreger |
| Summary: | Acute graft-versus-host disease (GVHD) is a major complication of allogeneic stem cell transplantation (SCT) and can be readily controlled by systemic high-dose steroids in many patients. However, patients whose GVHD is refractory to this therapy have a poor prognosis. Refractory patients have ongoing end-organ damage despite effective immunosuppression with second-line regimens, suggesting pathomechanisms independent from the initiating T-cell attack. To explore whether endothelial damage might contribute to GVHD refractoriness and to study the role of angiopoietin-2 (ANG2) in this process, we have compared kinetics of T-cell activation markers and markers of endothelial dysfunction in the serum of patients with sensitive (n = 23) and refractory GVHD (n = 25). Longitudinal measurements of soluble FAS ligand along with other immune markers demonstrate that refractory patients are not exposed to an overwhelming or unresponsive T-cell attack. However, in contrast to sensitive GVHD, refractory GVHD was associated with rising thrombomodulin levels and high ANG2/ vascular endothelial-derived growth factor ratios. Patients with refractory GVHD showed significantly increased ANG2 levels already before SCT. These results suggest that endothelial cell vulnerability and dysfunction, rather than refractory T-cell activity, drives treatment refractoriness of GVHD and opens new avenues for prediction and control of this devastating condition. |
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| Item Description: | Gesehen am 15.11.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2011-02-334821 |