Coincidence of cellular and antibody mediated rejection in heart transplant recipients – preliminary report

Antibody mediated rejection (AMR) can significantly influence the results of orthotopic heart transplantation (OHT). However, AMR and cellular rejection (CR) coexistence is poorly described. Therefore we performed a prospective pilot study to assess AMR/CR concomitance in endomyocardial biopsies (EMBs) obtained electively in 27 OHT recipients (21 M/6 F, 45.4 ± 14.4 y/o). Biopsy samples were paraffin embedded and processed typically with hematoxylin/eosin staining to assess CR, and, if a sufficient amount of material remained, treated with immunohistochemical methods to localize particles C3d and C4d as markers of antibody dependent complement activation. With this approach 80 EMBs, including 41 (51%) harvested within the first month after OHT, were qualified for the study. Among them 14 (18%) were C3d+, 37 (46%) were C4d+, and 12 (15%) were both C3d and C4d positive. At least one C3d+, C4d+, and C3d/C4d+ EMB was found in 10 (37%), 17 (63%), and 8 (30%) patients, respectively. Among 37 CR0 EMBs C3d was observed in 4 (11%), C4d in 17 (46%), and both C3d/C4d in 3 (8%) cases. Among 28 CR1 EMBs C3d was observed in 3 (11%), C4d in 11 (39%), and C3d/C4d in 3 (11%) cases. Among 15 CR2 EMBs C3d was observed in 7 (47%), C4d in 9 (60%), and C3d/C4d in 6 (40%) cases. Differences in C3d and C3d/C4d occurrence between grouped CR0-1 EMBs and CR2 EMBs (7/65 - 11% vs. 7/15 - 47%; 6/65 - 9% vs. 6/15 - 40%) were significant (p = 0.0035 and p = 0.0091, respectively, χ(2) test). In conclusion, apparently frequent CR and AMR coexistence demonstrated in this preliminary study warrants further investigation in this field.