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:

  1. AMR is a “clinical entity with specific histopathologic, immunopathologic, and serological characteristics.”
  2. 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.
  3. It may present hyperacutely (within 0-7 days after transplantation), early (within the first month after transplantation), or late (months to years after transplantation).
  4. 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.
  5. The presentation of AMR may vary from mild heart failure to cardiogenic shock.
  6. Endomyocardial biopsy is the gold standard for establishing the development of AMR.
  7. 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.
  8. 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.
  9. 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).
  10. AMR is associated with allograft failure, increased mortality, increased incidence of coronary artery vasculopathy, and overall poor prognosis.

Clinical Topics: Cardiac Surgery, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Lipid Metabolism, Novel Agents, Acute Heart Failure, Heart Transplant

Keywords: Adrenal Cortex Hormones, Allografts, Transplantation Tolerance, Antibodies, Antibodies, Monoclonal, Biopsy, Boronic Acids, Capillaries, Complement System Proteins, Coronary Vessels, Endothelium, Vascular, Fibrin, Graft Rejection, Heart Failure, Heart Transplantation, Immunoglobulins, Intravenous, Lymphatic Irradiation, Macrophages, Muromonab-CD3, Mycophenolic Acid, Photopheresis, Plasma Cells, Reoperation, Risk Factors, Shock, Cardiogenic, Staining and Labeling, T-Lymphocytes

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