Discordance between immunofluorescence and immunohistochemistry C4d staining and outcomes following heart transplantation.

Abstract

Capillary deposition of C4d is an important marker of antibody-mediated rejection (AMR) following heart transplantation (HT). There are two immunopathologic assay methods for detecting C4d: frozen-tissue immunofluorescence (IF) and paraffin immunohistochemistry (IHC). The clinical significance of discrepancy between the results of IF and IHC has not been understood. We reviewed 2187 biopsies from 142 HT recipients who had biopsies with assessment of both IF and IHC staining. Among them, 103 (73%) patients had negative IF and IHC C4d staining (Negative Group) and 32 (23%) patients had positive IF but negative IHC staining (Discordant Group). At the time of positive biopsy, 6 (19%) Discordant patients had graft dysfunction, compared to 5 (5%) Negative patients (p=.022). Cumulative incidence of cellular rejection at 1year was comparable (31% vs. 29%, p=.46); however, cumulative incidence of AMR was significantly higher in the Discordant group (21% vs. 4%, p=.004). Overall 1-year survival was comparable (90% vs. 96%, p=.24); however, freedom from heart failure (HF) was significantly lower in the Discordant group (70% vs. 96%, p<.001). The Discordant group showed higher rates of graft dysfunction, AMR and HF admission than the Negative group.