Controversies in defining cardiac antibody-mediated rejection: Need for updated criteria

Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation

“…Evidence across solid-organ transplantation suggests that AMR confers worse long-term outcomes and predisposes to chronic allograft dysfunction. [30][31][32][33][34][35] Prevention and treatment of AMR requires optimization to prevent long-term graft loss.…”

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

“…8 -18 As recognition of the presence of AMR becomes commonplace, a critical need to develop common definitions, standardized workup of biopsies, and reproducible diagnostic criteria and answer key questions has emerged. 19,20 In 2005, the ISHLT revised the 1990 working formulation for the standardization of heart transplant rejection. 2 An important component of this revision was the official recognition of AMR as a distinct rejection entity, which included histologic parameters, such as activated endothelial cells and intravascular macrophages, immunphenotypic evidence of capillary C4d deposition, and correlation with clinical parameters such as graft dysfunction and serologic evidence of donor-specific antibody production.…”

Current and future challenges in therapy for antibody-mediated rejection

“…1 Characterized by host antibodies targeting human leukocyte antigen (HLA) molecules, blood group antigens, and endothelial cells in the donor tissue, 2 the long-term effects are not fully understood. Although pioneering work on AMR by Hammond et al 3 was described in 1989, AMR failed to be recognized as a definite entity until 2005, when it was included in the rejection nomenclature.…”

“…4,5 AMR is a significant risk factor for poor outcomes after organ transplantation and is associated with, increased mortality, increased graft loss, and accelerated allograft coronary artery disease. [1][2][3][4][5][6] Risk factors for AMR include prior antibody exposure, multiparity, repeat transplantation, blood transfusions, use of ventricular assist devices, positive B-cell flow cytometry crossmatch, and elevated panel-reactive antibodies. AMR appears to be on the rise, likely secondary to changing trends in clinical practice, including selection of patients for transplantation on mechanical circulatory support and the development of more effective combinations of immunosuppressive drugs against acute cellular rejection (ACR).…”

“…Pulse steroid therapy has been shown to increase left ventricular function in patients with noncellular rejection. [1][2][3][4][5][6]11 Suppression of T lymphocytes T lymphocytes are a favored target of many of the current treatment protocols. B-lymphocyte activation requires Tlymphocyte-dependent stimulation to induce memory B lymphocytes, isotype switching, and production of highaffinity antibodies.…”