Antibody-mediated rejection in post-liver transplant clinical care: Are we there yet for timely diagnosis and treatment? - 07/08/24

Doi : 10.1016/j.liver.2024.100236 
Kevin H. Toomer a, Ahmet Gurakar b, Kiyoko Oshima a,
a Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 
b Section of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA 

Corresponding author at: Department of Pathology, Johns Hopkins Medical Institutions, Weinberg Building Room 2333, 401 N. Broadway, Baltimore, MD 21231, USA.Department of PathologyJohns Hopkins Medical InstitutionsWeinberg Building Room 2333, 401 N. BroadwayBaltimoreMD21231USA

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Highlights

With improving duration of survival after liver transplantation, antibody-mediated rejection (AMR) has been recognized as a significant contributor to allograft damage and long-term morbidity.
The numerous tolerogenic mechanisms operating within the hepatic microenvironment produce an intrinsic resistance to inflammatory injury; consequently, manifestations of AMR in the liver tend to be less overt and severe than at other sites.
Despite significant progress in recent years (in particular, the Banff 2016 criteria) diagnosis of AMR in the liver remains challenging due to nonspecific clinical and histopathologic features.
There is urgent need to identify new clinical and histologic AMR biomarkers to improve diagnosis, stratify patient risk, and inform therapy; molecular genetic approaches will likely be crucial to these efforts.
Clinical and laboratory evidence has shown that liver transplantation can protect other concurrently transplanted solid organs from immune-mediated injury; it may therefore be possible to harness tolerogenic effects of the liver in the creation of novel immune-modulating therapies.

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Abstract

With improvements in medical management and surgical technique in the field of solid organ transplantation, many historically prominent causes of liver allograft injury have been ameliorated or, in the case of Hepatitis C virus, eliminated altogether. In this transformed clinical landscape, antibody-mediated rejection (AMR) has emerged as a defining barrier to maintenance of long-term liver allograft function. The liver's unique anatomy, high regenerative capacity, and tolerogenic immunological environment tend to mitigate the severest AMR manifestations. Consequently, the clinical importance of AMR in the liver has been recognized more slowly than for other solid organ allografts. Significant strides have been made in elucidating clinical and histopathologic features of acute and chronic liver AMR, with the Banff 2016 criteria among the most notable. However, current histopathologic definitions of AMR are lacking in sensitivity and specificity. C4d staining is an imperfect biological surrogate for antibody-mediated injury, and suffers from significant technical limitations. The frequent co-occurrence of T cell mediated rejection and non-immunologic allograft damage (including recurrence of primary disease) also hinders definitive identification of AMR and results in misattribution of its effects. The goal of this review is to summarize the current understanding of AMR in the context of liver transplantation, including risk factors, pathogenesis, and current diagnostic and treatment strategies. Potential directions of future research are also addressed.

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Keywords : Liver, Transplantation, Antibody-mediated rejection

Abbreviations : ADCC, AIH, APC, AMR, DSA, FFPE, HCV, HLA, IF, IHC, IVIG, MAC, MSC, PD-L1, SAB, TCMR, TGF-β, Treg


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Vol 16

Article 100236- novembre 2024 Retour au numéro
Article précédent Article précédent
  • Going with the flow: High-flow nasal cannula for management of post-transplant hypoxemia in hepatopulmonary syndrome
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| Article suivant Article suivant
  • Short-term alcohol abstinence prior to liver transplantation and impact on rejection
  • Kaitlyn Legg, Tracy Sparkes, Ian Booth, Daniel Maluf, Chandra Bhati, Neha Jakhete, Sari Freedman

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