Endothelial damage is aggravated in acute GvHD and could predict its development

Area of Science:

• Hematology
• Immunology
• Vascular Biology

Background:

• Acute graft-versus-host disease (aGvHD) is a major complication following allogeneic hematopoietic cell transplantation (allo-HCT).
• Endothelial cells play a critical role in the pathophysiology of aGvHD, but the extent of endothelial dysfunction and potential biomarkers remain under investigation.

Purpose of the Study:

• To investigate enhanced endothelial dysfunction in patients developing aGvHD post-allo-HCT.
• To identify biomarkers with predictive or diagnostic value for aGvHD.

Main Methods:

• In vitro experiments exposed endothelial cells (ECs) to patient serum to assess surface adhesion receptors, extracellular matrix reactivity (VWF, platelet adhesion), and intracellular signaling.
• Plasma levels of VWF, ADAMTS-13, TNFR1, sVCAM-1, and sICAM-1 were measured in patients.

Main Results:

• In vitro, ECs exposed to aGvHD serum exhibited a more proinflammatory and prothrombotic phenotype.
• Elevated plasma levels of VWF and TNFR1 at day 7 post-allo-HCT independently or combined, could predict aGvHD development in approximately 90% of patients.

Conclusions:

• Endothelial damage is exacerbated in allo-HCT recipients who develop aGvHD.
• VWF and TNFR1 are promising biomarkers for the prediction of aGvHD, potentially improving understanding and management of this complication.