Steroid-refractory GVHD

• Verfasst von: Luft, Thomas [VerfasserIn]
• Verfasst von: Dietrich, Sascha [VerfasserIn]
• Verfasst von: Falk, Christine [VerfasserIn]
• Verfasst von: Conzelmann, Michael [VerfasserIn]
• Verfasst von: Hess, Michael [VerfasserIn]
• Verfasst von: Benner, Axel [VerfasserIn]
• Verfasst von: Neumann, Frank [VerfasserIn]
• Verfasst von: Isermann, Berend [VerfasserIn]
• Verfasst von: Hegenbart, Ute [VerfasserIn]
• Verfasst von: Ho, Anthony Dick [VerfasserIn]
• Verfasst von: Dreger, Peter [VerfasserIn]
• Titel: Steroid-refractory GVHD
• Titelzusatz: T-cell attack within a vulnerable endothelial system
• Verf.angabe: Thomas Luft, Sascha Dietrich, Christine Falk, Michael Conzelmann, Michael Hess, Axel Benner, Frank Neumann, Berend Isermann, Ute Hegenbart, Anthony D. Ho, and Peter Dreger
• Jahr: 2011
• Umfang: 8 S.
• Fussnoten: Gesehen am 15.11.2022
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 2011
• Band/Heft Quelle: 118(2011), 6, Seite 1685-1692
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood-2011-02-334821
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1822641551

Abstract

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.