Antibody-Mediated Rejection: AHA Scientific Statement | Ten Points to Remember
- Colvin MM, Cook JL, Chang P, et al.
- Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management: A Scientific Statement From the American Heart Association. Circulation 2015;Apr 2:[Epub ahead of print].
The following are 10 points to remember from this American Heart Association Scientific Statement about antibody-mediated rejection (AMR) in cardiac transplantation:
- AMR is a “clinical entity with specific histopathologic, immunopathologic, and serological characteristics.”
- Risk factors for AMR include: elevated PRA, CMV seropositivity, prior mechanical circulatory support, prior treatment with muromoab-CD3 and development of antibodies against mouse monoclonal muromonab-CD3, history of retransplantation, multiparity, and positive crossmatch on T-cell flow cytometery.
- It may present hyperacutely (within 0-7 days after transplantation), early (within the first month after transplantation), or late (months to years after transplantation).
- Key diagnostic findings include: a) Clinical evidence of graft dysfunction, b) histopathologic evidence of acute capillary injury including changes in capillary endothelium and macrophages in capillaries, c) immunopathologic evidence for antibody-mediated injury including changes in C3d and/or C4d immunofluorescence staining or CD68 or C4d immunoperoxidase staining or severe fibrin in vessels, and d) serological evidence of anti-HLA or anti-donor antibodies.
- The presentation of AMR may vary from mild heart failure to cardiogenic shock.
- Endomyocardial biopsy is the gold standard for establishing the development of AMR.
- There have been no large randomized clinical trials to evaluate therapies for AMR and hence there are no level I recommendations and all recommendations are therefore based on consensus.
- The guiding principles for the management of AMR include removing circulating alloantibodies, reducing production of additional antibodies, and suppressing T-cell and B-cell responses.
- Commonly used agents utilized in the treatment of AMR include: a) corticosteroids (act by suppression of T- and B-cell response), b) plasmapharesis (acts by eliminating circulating antibodies), c) IVIG (act by inhibiting residual antibodies and inhibition of complement), whereas less commonly used agents include: a) rituximab or splenectomy (act by suppression or depletion of B cells), b) bortezomib (act by suppression or depletion of plasma cells), c) eculizumab (by inhibition of complement), and d) mycophenolate mofetil, anti-lymphocyte antibodies, photopheresis, or total lymphoid irradiation (these act by suppression of T-cell response). In addition to treating AMR with cytotoxic or antibody-directed therapy, the background regimen should be optimized using potent B-cell receptors (mycophenolate and sirolimus).
- AMR is associated with allograft failure, increased mortality, increased incidence of coronary artery vasculopathy, and overall poor prognosis.
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