**7. Markers of antibody mediated rejection**

#### **7.1. Histopathologic detection of C4d**

Feucht et al. (Feucht et al., 1993) in Munich showed that peritubular capillary (PTC) C4d deposition in renal transplant biopsies is strongly associated with a poor prognosis and raised the possibility that antibodies were responsible. Currently, C4d has been adopted as a marker of antibody-mediated rejection (Racusen et al., 2003). The justification for the selection of C4d, a split product of C4, as a marker for AMR comes from its position in the cascade of complement activation. C4d, a split product of the classical pathway of complement activation, is present covalently bound on tissue near the sites of complement activation by alloantibody, e.g., vascular endothelial cell membrane.

C4d deposition in renal peritubular capillaries is strongly associated with circulating antibody to donor HLA class I or class II antigens (Bohmig et al., 2002; Haas et al., 2006) and is currently the best single marker of complement-fixing circulating antibodies to the endothelium.
