[361] 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-514.3.1.4) 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.

Cox Hazaard Model for C3d and C4d Staining
n=% CV mortalityHR
C4d+ C3d+2080.52.47
C4d+ C3d-2292.612.0
C4d- C3d+2110.96.65
C4d- C3d-30700.31.0
CV: cardiovascular; HR: hazard ratio

Most biopsies (82%) were negative for both C4d and C3d and patients with this staining pattern had the lowest CVM. Compared to cases with C4d staining alone, those with both C4d and C3d deposition paradoxically had superior outcomes (hazard ratio = 0.18 among all C4d positive cases).
Conclusions: Detection of C3d in transplant endomyocardial biopsies is associated with a small but significant difference in cardiovascular mortality, adding clinically useful information to staining for C4d alone. Mediation by complement pathway regulators, indicated by the disparate staining patterns, may account for this difference, but further study is needed.
Category: Cardiovascular

Wednesday, March 24, 2010 1:00 PM

Poster Session VI # 33, Wednesday Afternoon

 

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