Antibody-Mediated Rejection in Heart Transplantation: Characterization of Patients with C4d Immunoreactivity in Endomyocardial Biopsies.
Muhammad K Mirza, Savitri E Fedson, Yiqing Chi, Aliya N Husain. The University of Chicago, IL
Background: C4d is widely accepted as a marker for antibody-mediated rejection in cardiac allografts; however its usefulness as a prognostic marker is under debate. The aim of this prospective study was to determine the significance of C4d immunoreactivity in endomyocardial biopsies by correlating with cardiac dysfunction, cardiac allograft vasculopathy (CAV) and death.
Design: 1771 biopsies from 200 heart transplant patients were stained prospectively by IHC for C4d deposition on paraffin-embedded tissue using anti-human C4d polyclonal antibody. Strong diffuse endothelial staining was considered positive. Cardiac dysfunction at the time of positive biopsy was evaluated by echocardiography and intracardiac filling pressures. Patients were followed for 1-6 years.
Results: Positive staining of C4d was present in 43 biopsies (2.4%) from 25 patients (12.5%). The average time from transplant to the first episode of C4d positivity was 365 days (ranging from 8 to 986 days). 9 patients had clinically significant cardiac dysfunction at the time of positive biopsy (13 out of 43 positive biopsies). 14 patients (7%) died, 7 of whom (50%) had cardiac dysfunction at the time of positive biopsy. Autopsy was performed on 6 patients; in this subset, mean time duration between transplant and death was 1213 days (ranging from 66 to 2110 days) and between first episode of C4d positivity and death was 640 days (ranging from 2 to 1193 days). CAV was noted in all 6 patients (100%).
Conclusions: C4d positivity correlated with poorer outcomes. 14 out of 25 patients who showed C4d positivity died (56%) (Institutional 5-year post-transplant survival is 78%). The outcome is even worse when C4d positivity is associated with cardiac dysfunction (100% mortality).
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 43, Wednesday Afternoon