Circulating alloantibodies encounter the grafted endothelium as the first target. Living endothelial cells can rapidly eliminate bound antibodies from the cell surface by “capping”, “shedding” or “internalisation”. C4d is the degradation product of the activated complement factor C4, a component of the classical complement cascade, which is typically initiated by binding of antibodies to specific target molecules. Detection of C4d is regarded as an indirect sign, a “footprint” of an antibody response against the allograft. The majority of publications describe C4d as an important biomarker in kidney transplantation but also in heart, liver, and other transplants. Organ transplantation Kidney transplantation Liver transplantation Heart transplantation Lung transplantation