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Antibody-Mediated Rejection: A Review
#MMPMID28331448
Garces JC
; Giusti S
; Staffeld-Coit C
; Bohorquez H
; Cohen AJ
; Loss GE
Ochsner J
2017[Spr]; 17
(1
): 46-55
PMID28331448
show ga
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). CONCLUSION: 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.
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