Deposition of C4d and C3d in cardiac transplants: A factor in the development of coronary artery vasculopathy

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

“…25,35,42,45 The literature is also limited on the role of C3d in addition to C4d in evolution of cardiac AMR (Table 4). 15,26,27,40 Despite different approaches, centers using paraffin IC arrive at similar C4d staining conclusions. 20,46 The smaller number of centers additionally staining paraffin sections for C3d showed similar concordance.…”

“…28,29 Combined forms of AMR and ACR have been recognized, that may also increase susceptibility to cardiac allograft vasculopathy. 12,15 Recent reports have also highlighted diversity of approaches to the biopsy specimen investigation and diag- nosis of AMR amongst pathologists. 19,20,23,30 Further, it is likely that AMR evolves along a worsening spectrum of pathologic changes analogous to ACR.…”

“…31 The conference concluded that there was a morphologic and immunophenotypic spectrum of AMR-related changes. These may range 15 IP 0-3ϩϩϩ 0 ϭ neg All fragments Ͼ2 1 ϭ weak and few areas (focal) 2 ϭ moderate, several areas (multifocal) 3 ϭ strong and diffuse Fedrigo (2010) 16 IP 0-3ϩϩϩ 0 ϭ neg All fragments 2-3 1 ϭ focal weak 2 ϭ multifocal and moderate 3 ϭ diffuse and strong Miller (2010) 45 IF vs IP IP 0-3ϩϩϩ 0 ϭ absent or focal IF-1 fragment from archives; IP-all fragments from latent AMR (serologic evidence of donor-specific antibodies) to silent AMR (deposition of C4d in capillaries of otherwise normal myocardium) to subclinical (or asymptomatic) AMR (combining the above 2 scenarios with tissue damage but no graft dysfunction) to full-blown AMR with a "full house," including allograft dysfunction. However, some uncertainty in conclusively establishing this notion of a longitudinal and progressive spectrum remains to this day.…”

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.…”

Intentional ABO-incompatible heart transplantation: A case report of 2 adult patients

“…Deposition of C4d in cardiac transplants has been associated with the development of coronary artery vasculopathy and poor outcome. [12][13][14] Therefore, long-term follow-up of the patients is extremely important. With ABO-compatible transplantation as the first choice and ABO-incompatible transplantation as the second choice in highly selected patients according to our strategy, an optimal match of every available organ may be achieved.…”