Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart …

MM Colvin, JL Cook, P Chang, G Francis, DT Hsu… - Circulation, 2015 - Am Heart Assoc
MM Colvin, JL Cook, P Chang, G Francis, DT Hsu, MS Kiernan, JA Kobashigawa…
Circulation, 2015Am Heart Assoc
The success of heart transplantation in the 1980s was enabled by the ability to diagnose
rejection by transjugular right ventricular endomyocardial biopsy, a technique developed by
Philip Caves in 1973. The diagnosis of acute cellular rejection (cytotoxic T-cell mediated) is
made by histological identification of interstitial leukocyte infiltration with various degrees of
myocyte damage. These features are sensitive and specific and correlate with allograft
dysfunction. Furthermore, this immunopathologic and clinical state responds to anti–cellular …
The success of heart transplantation in the 1980s was enabled by the ability to diagnose rejection by transjugular right ventricular endomyocardial biopsy, a technique developed by Philip Caves in 1973. The diagnosis of acute cellular rejection (cytotoxic T-cell mediated) is made by histological identification of interstitial leukocyte infiltration with various degrees of myocyte damage. These features are sensitive and specific and correlate with allograft dysfunction. Furthermore, this immunopathologic and clinical state responds to anti–cellular rejection therapies with clinical improvement and resolution of histological rejection features. The subset of heart transplant recipients with graft failure and no evidence of cellular rejection were considered to have biopsy-negative rejection. Pathological changes observed in this setting were not included in the histological grading systems for cellular rejection, and these collective pathological changes were variably referred to as humoral, vascular, or antibody-mediated rejection (AMR). The first limited description of humoral rejection was included in the 1990 ISHLT criteria defined as positive immunofluorescence, vasculitis, or severe edema in the absence of cellular infiltrate5 (Table 2). By the time of the 2004 ISHLT revision, the immunologic process underlying AMR was better described in the literature. 6 Routine screening was still not advocated; however, a recommendation was made for every endomyocardial biopsy specimen to undergo histological evaluation for AMR. At that time, the classification AMR 0 was assigned in the absence of histological or immunopathologic features. Confirmation of AMR or AMR 1 was defined as histological evidence with identification of antibodies (directed against CD68, CD31, C4d) and serum presence of donor-specific antibody (DSA; Table 2). With the publication of the 2004 working formulation, the field moved toward almost exclusive use of the term AMR and use of more precise histological descriptors. In 2006, the ISHLT Immunopathology Task Force provided an expanded description of the histological evidence of acute capillary injury, the minimum requirement for immunopathologic evidence of antibody-mediated injury, and an improved definition of serological evidence of circulating antibodies1 (Table 1). The persistent variations in the diagnosis and treatment of AMR were addressed in 2 related conferences: the Heart Session of the Tenth Banff Conference on Allograft Pathology (August 2009) and the ISHLT Consensus Conference on AMR (April 2010). These sessions undertook another revision in an attempt to refine the immunopathologic assessment of AMR. Our increased understanding of the pathological processes behind AMR enabled an evolution beyond the descriptive “biopsy-negative rejection” to AMR, a clinical entity with specific histopathologic, immunopathologic, and serological characteristics.
Am Heart Assoc