Role of the complement system in rejection.

The complement system plays a complex role in transplantation, beginning with effects on reperfusion injury and continuing with stimulation of the adaptive immune response. Recent evidence has emphasised the importance of the late components of the complement cascade in the mediation of post-ischaemic damage, which are apparently triggered by the classical, alternative or lectin pathways of complement activation, depending on the organ affected. In studies of renal allograft rejection, the local synthesis of complement component C3 seems to influence the T-cell response more strongly than circulating complement protein, raising the possibility that there is co-operation between locally derived C3 and antigen presentation in the graft. Class switching of alloantibody to a high-affinity IgG response is also highly dependent on C3. In addition, the finding that capillary-bound C4d is a robust marker for humoral rejection has started a new investigation into the significance of alloantibodies in acute and chronic allograft rejection. There are several selective and nonselective inhibitors suitable for clinical development; clearly it is time for more concerted effort to evaluate their role in clinical transplantation.