C4D Immunostaining in Surveillance Endomyocardial Biopsies From Well-Functioning Heart Allografts

Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management

“…[23][24][25] Currently, C4d is used frequently to diagnose AMR, and some authors suggest that C4d can be used as an immunopathologic surrogate for AMR. [25][26][27][28][29][30][31][32] C4d positivity is also used in combination with histological features-with circulating DSA, or clinical graft dysfunction. 23,[33][34][35][36] Depending on how restrictive the pathological definition of AMR is (ie, number of criteria required), the reported incidence varies, with lower reported incidence with more criteria required.…”

“…In this study, the diagnosis of AMR was based on demonstration of capillary endothelial cell swelling, interstitial hemorrhage, interstitial edema and neutrophil infiltration, the presence of CD68 + macrophages within capillary cells, and Immunopathology was conducted only on cases with suspicious histopathology or on clinical request. The following sets in parentheses represent multiple manuscripts from the same institutional transplantation program: (1, 2, 5, 18, 22); (10,11,24,29); (28,33,34); (7,15,23); (3,26); (12,13); (14,20).…”

The ISHLT working formulation for pathologic diagnosis of antibody-mediated rejection in heart transplantation: Evolution and current status (2005–2011)

“…The significance of perimyocytic staining as reported in a small number of IF studies were not discussed due to the time constraints placed on the breakout session. 17,27 B. Surveillance and frequency of immunopathological assessment (a) Initial immunostaining The initial studies from Utah reported that cases of AMR typically occurred within the first 8 weeks after transplant. 3,21,47 Currently, a diverse range of protocols are used, ranging from centers that do not follow any immunostaining schedule to centers that perform immunostaining on every surveillance biopsy specimen to centers that stain only emergent specimens.…”

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

“…It should be easier in the presence of myocardial damage (observed in CR2 cases), but still it can be questionable in the absence of transplanted heart failure features. The presence of C4d deposits in stable long-term survivors, described by many authors [ 18 , 19 ], also puts in doubt its role as a marker of treatment-requiring rejection. The choice of C3d and C4d as markers of AMR seems to be the best anchored in the literature [ 5 , 20 ]; however, current guidelines underline the role of macrophage antigen staining to establish the AMR diagnosis when using paraffin section immunohistochemistry [ 4 , 21 ], which was not performed as part of this study.…”