Abstract
Antibody-mediated rejection (AMR) is gaining increasing recognition as a major complication after heart transplantation, posing a significant risk for allograft failure, cardiac allograft vasculopathy, and poor survival. AMR results from activation of the humoral immune arm and the production of donor-specific antibodies (DSA) that bind to the cardiac allograft causing myocardial injury predominantly through complement activation. The diagnosis of AMR has evolved from a clinical diagnosis involving allograft dysfunction and the presence of DSA to a primarily pathologic diagnosis based on histopathology and immunopathology. Treatment for AMR is multifaceted, targeting inhibition of the humoral immune system at different levels with emerging agents including proteasome and complement inhibitors showing particular promise. While there have been significant advances in our current understanding of the pathogenesis, diagnosis, and treatment of AMR, further research is required to determine optimal diagnostic tools, therapeutic agents, and timing of treatment.
Highlights
Antibody-mediated rejection (AMR) is a diagnostic and therapeutic challenge in human heart transplantation
AMR results from activation of the humoral immune arm and the production of donor-specific antibodies (DSA) that bind to the cardiac allograft causing myocardial injury predominantly through complement activation
The diagnosis of AMR has evolved from a clinical diagnosis involving allograft dysfunction and the presence of DSA to a primarily pathologic diagnosis based on histopathology and immunopathology
Summary
Antibody-mediated rejection (AMR) is a diagnostic and therapeutic challenge in human heart transplantation. The true incidence of AMR is unknown, it has been reported in 10–20% of patients after heart transplant, typically occurring within a few months after transplant [1, 2]. Not uncommon with one study reporting 25% of AMR cases occurring more than one year after transplantation [1]. AMR was first described as a clinical entity in 1987 by Herskowitz et al who identified a subset of heart transplant patients with arteriolar vasculitis and poor outcomes [4]. In 2005, the International Society for Heart and Lung Transplant (ISHLT) published specific guidelines for the diagnosis of AMR [6]. This paper will discuss the current understanding of AMR, focussing on pathogenesis, diagnosis, and treatment
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