Vascular endothelium as ‘novel’ target of graft-versus-host disease

There is increasing evidence of the existence of an endothelial form of graft-versus-host disease (GvHD). The early endothelial injury syndromes – transplant-associated microangiopathy (TAM), veno-occlusive disease (VOD) of the liver, diffuse alveolar hemorrhage, engraftment syndrome, and capillary leak syndrome – all share common features with acute GvHD. They are more likely to occur after allogeneic hematopoietic stem-cell transplantation (HCT), in unrelated transplantation, or with non-T-cell-depleted grafts. In addition, acute GvHD is a risk factor for all these endothelial syndromes. Chronic GvHD leads to a rarefaction of microvessels caused by the infiltration of alloreactive cytotoxic T lymphocytes. Furthermore, late cardiovascular accidents are more likely to occur in patients treated with allogeneic than autologous HCT, suggesting that an immunological mechanism is involved in the development of atherosclerosis. Finally, biomarkers of endothelial injury show a close relationship with GvHD. These data support the notion that early endothelial damage syndromes, atherosclerosis, and vascular endothelial GvHD share a common denominator in patients treated with allogeneic HCT.