Dendritic reticulum cells retain C4d: tonsil provides a useful control tissue.
Capillary endothelium in humoral rejection. Acute cellular rejection is identifiable on H/E sections. In addition, a humoral response to donor antigens is known to occur but is difficult to demonstrate in routine practice. Studies have variously been performed on frozen sections by an indirect immunofluorescence technique1 and on paraffin-embedded tissue2.
In the early transplanted kidney, linear deposition of C4d occurs along peritubular capillaries in association with transplant glomerulitis: C4d deposition correlates with tubular MHC class II expression, panel-reactive antibody titers and raised serum creatinine levels at the time of biopsy. Arteries do not show C4d deposition. Aggressive antirejection therapy in instances of C4d-positive acute cellular rejection episodes may be beneficial. A second group of C4d-positive patients present with only mild allograft dysfunction and no histological signs of rejection: these patients patients did not show histological features suggestive of an antibody mediated type of rejection [i.e. no prominent polymorphonuclear leukocytes in peritubular capillaries and no fibrin thrombi] and do not appear to significantly benefit from antirejection therapy1.
In renal allograft biopsies more than twelve months after transplantation, endothelial C4d deposition was found to be associated with contemporaneous or subsequent chronic transplant glomerulopathy, with basement membrane multilayering in peritubular capillaries and with an accumulation of mononuclear inflammatory cells (but not granulocytes) in peritubular capillaries2.
In cardiac allografts, deposition of C4d in capillaries, accompanied by fibrin deposition, is predictive of graft loss and appears to be useful for the identification of patients with humoral rejection in need to modified immunosuppressive therapy. In a study of patients less than three months post-transplantation, only one of the five biopsies with C4d+++ also showed grade 3a cellular rejection3.
In liver transplants, C4d may identify a small subgroup of individuals in whom chronic humoral microvascular injury contributes to allograft dysfunction4.
Identification of humoral rejection after renal, cardiac or liver transplantation.
References
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
This page last revised 18.5.2007.
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