Are anti-endothelial cell antibodies a pre-requisite for the acute vascular rejection of xenografts?

Background : Vascular rejection occurring within the first few weeks after transplantation is still the major immunological barrier to the long term survival of xenografts. Currently there is no consensus about what to call this type of rejection (acute vascular rejection, delayed xenograft rejection or acute humoral xenograft rejection), nor about how to prevent or treat it. Methods : A review of published evidence to define the heterogeneity of this phase of rejection and examine the role of antibodies, complement and graft-infiltrating inflammatory cells. Results : i) antibodies are always involved in acute vascular rejection; ii) this antibody-mediated rejection may be complement-dependent or -independent; iii) inflammatory cells may mediate an antibody- and complement-independent phase of rejection in some small animal models (which, in its pure form cannot be called 'vascular rejection') iv) there remain significant questions about the relevance of 'accommodation' and the importance of coagulation abnormalities. Conclusions : Without doubt, future research would be helped by distinguishing between these different forms of delayed xenograft rejection, using terminology to reflect the involvement of specific pathophysiological mechanisms. An updated classification of the stages of xenograft rejection is proposed here.