Antibody-mediated rejection.
OBJECTIVE
The diagnosis of antibody-mediated rejection (AMR) has been revolutionized in recent years by advances in the detection of human leukocyte antigen (HLA) and non-HLA antibodies and by the standardized classification of histologic and immunologic changes in endomyocardial biopsies. The treatment of AMR is also undergoing significant development with targeted use of therapies directed at antibody production and function.


RESULTS
The diagnosis of AMR achieved greater standardization after a consensus conference in 2010. By the proposed classification, endomyocardial biopsies are now graded on the basis of the severity of histologic and immunologic changes. Management of AMR is often complicated, as patients may have persistent symptoms after treatment, including a reduction in ejection fraction, restrictive physiology leading to recurrent heart failure, and accelerated progression of transplant coronary artery disease. We often rely on therapies to reduce the levels of donor-specific anti-HLA antibodies, including rituximab and bortezomib, as well as photopheresis to alter the function of T cells, although such patients may go on to require redo transplantation.


CONCLUSIONS
AMR offers challenges of diagnosis and management, but recent advances in the detection of antibodies, the interpretation of endomyocardial biopsies, and the use of therapies directed toward antibody production offer great promise. In the future, standardization of management across transplant centers will allow for clinical trials of the effectiveness of these therapies.
Cedars-Sinai Heart Institute, Los Angeles, California, USA.
Michelle M
MM
Kittleson
Jon A
JA
Kobashigawa
D000906:Antibodies / Q000276:immunology*; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016377:Organ Transplantation / Q000009:adverse effects* / Q000379:methods*; D014181:Transplantation Immunology
D000906:Antibodies; D006680:HLA Antigens