Additional Prognostic Contribution of C3d Staining in Antibody Mediated Rejection of Cardiac Allografts
DV Miller, MP Revelo, J Isaac, AG Kfoury, J Stehlik, GL Snow, ME Hammond. Utah Transplant Affiliated Hospitals (UTAH) Cardiac Transplant Program, Salt Lake City, UT; Intermountain Health Care, Salt Lake City, UT
Background: Antibody mediated rejection (AMR) of cardiac allografts is a complex immunologic process initiated by antibodies directed against antigens expressed on donor endothelium. Ensuing events lead to the pathologic hallmarks of AMR in the acute phase (complement activation and macrophage accumulation). Staining for complement component C4d is the mainstay for detecting complement activation in endomyocardial biopsies because it persists in tissues by covalent binding. Staining for C3d ("downstream" from C4 in the complement cascade) is routinely performed at some institutions in combination with C4d, but there are few studies addressing the additive diagnostic and prognostic value of C3d deposition.
Design: The patient population was comprised of allograft recipients tracked in the Utah Transplant Affiliated Hospitals (UTAH) cardiac transplant database (28,450 biopsies on 986 patients). Results of immunofluorescence staining for C3d (AbD Serotec clone 053A-5126.96.36.199) and C4d (AbD Serotec clone 10-11) were scored on a 0, 0.5+ (trace), 1+, 2+, 3+ scale, and all data from the biopsies were prospectively recorded at the time of biopsy sign out. Scores of 1+ or greater were considered positive. A Cox proportional hazard model using the endpoint of cardiovascular mortality (CVM) was utilized to evaluate combinations of C3d and C4d staining.
Results: 3735 biopsies from 422 patients in the database had sufficient information to be included in the analysis. The data are summarized in the table below.
|n=||% CV mortality||HR|