C4d is a stable remnant of classical complement activation which becomes covalently bound to endothelium and basement membrane, rendering it persistent. It is generated via the classical antibody-induced pathway. Activated C1s cleaves C4 to release C4a into the circulation and C4b, which binds endothelium. The C4b is unstable, releasing C4c into the circulation and leaving bound C4d.

Polyvalent antiserum against C4d allows staining in paraffin sections.

Immunohistochemical expression

Diagnostic utility

Identification of humoral rejection after renal, cardiac or liver transplantation.


1 Nickeleit V, Zeiler M, Gudat F, et al. Detection of the complement degradation product C4d in renal allografts: diagnostic and therapeutic implications. J Am Soc Nephrol 2002; 13:242-51 FULL TEXT

2 Regele H, Bohmig GA, Habicht A, et al. Capillary deposition of complement split product C4d in renal allografts is associated with basement membrane injury in peritubular and glomerular capillaries: a contribution of humoral immunity to chronic allograft rejection. J Am Soc Nephrol 2002; 13:2371-80 FULL TEXT

3 Behr TM, Feucht HE, Richter K, et al. Detection of humoral rejection in human cardiac allografts by assessing the capillary deposition of complement fragment C4d in endomyocardial biopsies. J Heart Lung Transplant 1999; 18:904-12

4 Bellamy CO, Herriot MM, Harrison DJ, et al. C4d immunopositivity is uncommon in ABO-compatible liver allografts, but correlates partially with lymphocytotoxic antibody status. Histopathology 2007; 50:739-49

This page last revised 18.5.2007.

©SMUHT/PW Bishop