Controversy exists regarding the criteria used for the diagnosis of Antibody-mediated rejection (AMR) and a consensus has not been reached regarding the most appropriate criteria for the diagnosis. Recent data have suggested the use of Immunohistochemistry for the presence of C4d as being adequate for the diagnosis but has not been uniformly accepted. The added utility of C3d staining in addition to C4d is unknown.
METHODS:
We evaluated endomyocardial biopsies from consecutive patients collected over a 14 month period. Biopsies were screened for the presence of complement deposition, specifically C4d and C3d. Electronic medical records were reviewed retrospectively for the clinical data and the diagnosis of clinically relevant AMR.
RESULTS:
A total of 1511 endomyocardial biopsies were performed on 330 consecutive patients. Eighteen patients were found to have evidence of C4d complement staining and 18 patients with both C4d and C3d staining. Mortality was significantly higher (28% vs 0%, p < 0.05) in the patients with both C4d and C3d staining compared to C4d alone. Patients with both C4d and C3d received more treatment (corticosteroids, plasmapheresis), were hospitalized more frequently, and illness was associated with frank hemodynamic compromise including reduced EF and cardiac index (Table 1
).
CONCLUSION:
Complement deposition with both C4d and C3d on endomyocardial biopsy is more commonly associated with reduced EF, hemodynamic compromise, and mortality. C4d alone, although common, is often not associated with morbidity. Statregies for the management and follow up of AMR should be a priority for research.
TABLE 1:
Clinical Outcomes