Antibody-Mediated Rejection: A Review.
BACKGROUND
Chronic antibody injury is a serious threat to allograft outcomes and is therefore the center of active research. In the continuum of allograft rejection, the development of antibodies plays a critical role. In recent years, an increased recognition of molecular and histologic changes has provided a better understanding of antibody-mediated rejection (AMR), as well as potential therapeutic interventions. However, several pathways are still unknown, which accounts for the lack of efficacy of some of the currently available agents that are used to treat rejection.


METHODS
We review the current diagnostic criteria for AMR; AMR paradigms; and desensitization, treatment, and prevention strategies.


RESULTS
Chronic antibody-mediated endothelial injury results in transplant glomerulopathy, manifested as glomerular basement membrane duplication, double contouring, or splitting. Clinical manifestations of AMR include proteinuria and a rise in serum creatinine. Current strategies for the treatment of AMR include antibody depletion with plasmapheresis (PLEX), immunoadsorption (IA), immunomodulation with intravenous immunoglobulin (IVIG), and T cell- or B cell-depleting agents. Some treatment benefits have been found in using PLEX and IA, and some small nonrandomized trials have identified some benefits in using rituximab and the proteasome inhibitor-based therapy bortezomib. More recent histologic follow-ups of patients treated with bortezomib have not shown significant benefits in terms of allograft outcomes. Furthermore, no specific treatment approaches have been approved by the US Food and Drug Administration. Other agents used for more difficult rejections include bortezomib and eculizumab (an anti-C5 monoclonal antibody).


CONCLUSIONS
AMR is a fascinating field with ample opportunities for research and progress in the future. Despite the use of advanced techniques for the detection of human leukocyte antigen (HLA) or non-HLA donor-specific antibodies, alloimmune response remains an important barrier for successful long-term allograft function. Treatment of AMR with currently available therapies has produced a variety of results, some of them suboptimal, precluding the development of standardized protocols. New therapies are promising, but randomized controlled trials are needed to find surrogate markers and improve the efficacy of therapy.
Multi-Organ Transplant Institute, Ochsner Clinic Foundation, New Orleans, LA ; The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA.
Jorge Carlos
JC
Garces
Multi-Organ Transplant Institute, Ochsner Clinic Foundation, New Orleans, LA ; Department of Nephrology, Ochsner Clinic Foundation, New Orleans, LA.
Sixto
S
Giusti
The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA ; Department of Nephrology, Ochsner Clinic Foundation, New Orleans, LA.
Catherine
C
Staffeld-Coit
Multi-Organ Transplant Institute, Ochsner Clinic Foundation, New Orleans, LA ; The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA.
Humberto
H
Bohorquez
Multi-Organ Transplant Institute, Ochsner Clinic Foundation, New Orleans, LA ; The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA.
Ari J
AJ
Cohen
Multi-Organ Transplant Institute, Ochsner Clinic Foundation, New Orleans, LA ; The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA.
George E
GE
Loss
Desensitization–immunologic; HLA antigens; graft rejection; kidney transplantation; transplantation tolerance