The significance of C4d staining with minimal histologic abnormalities.
OBJECTIVE
C4d deposition within peritubular capillaries (PTCs) in renal allograft biopsies is a specific marker for interaction of antibody with the graft, and is an extremely useful tool for the diagnosis of antibody-mediated rejection (AMR). Whereas PTC C4d itself is not diagnostic of AMR, it is usually accompanied by histologic features of acute and/or chronic AMR. However, some biopsies, mainly from ABO-incompatible renal allografts, show C4d staining without histologic findings of AMR or cell-mediated rejection. The significance of such C4d staining remains a topic of debate, and this finding may have different implications in ABO-incompatible versus conventional renal allografts.


RESULTS
In biopsies of ABO-incompatible renal allografts (particularly protocol biopsies), C4d deposition in the absence of histologic evidence of rejection is a common finding, is not associated with an increased risk of graft scarring, and may even indicate a decreased risk of scarring, at least in the short term. By contrast, in positive cross-match and conventional renal allografts such C4d deposition is uncommon, and may indicate potentially reversible graft injury. However, a state of C4d staining without associated graft injury may be inducible in positive cross-match grafts by complement inhibition.


CONCLUSIONS
C4d staining without associated histologic findings of rejection may represent a marker for stable graft accommodation, at least in ABO-incompatible renal allografts. However, further studies are clearly needed to determine what the long-term implications of such C4d deposition are.
Haas
Mark
M
Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. mark.haas@cshs.org
D000017:ABO Blood-Group System; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001788:Blood Grouping and Crossmatching; D002196:Capillaries / Q000276:immunology / Q000473:pathology; D015935:Complement C4b / Q000378:metabolism*; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D010446:Peptide Fragments / Q000378:metabolism*; D011237:Predictive Value of Tests; D018570:Risk Assessment; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000017:ABO Blood-Group System; D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d