Antibody-mediated rejection in the liver allograft.

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There is increasing evidence to suggest that antibody-mediated mechanisms play a role in the pathogenesis of liver allograft rejection. This article will review the pathology of antibody-mediated rejection (AMR) focusing on recent studies which have improved our understanding of the clinicopathological features and diagnostic approaches.


Recent studies have investigated the patterns of immunohistochemical staining for C4d as a tissue marker of AMR in posttransplant biopsies, and have correlated these findings with other histopathological changes and with the presence of donor-specific antibodies (DSAs). These studies have highlighted the diagnostic applications and limitations of C4d immunostaining. They have also emphasized the importance of using strict criteria for defining 'pure' AMR in the liver allograft - that is, graft dysfunction associated with compatible histological findings (typically resembling biliary obstruction), the presence of DSAs and diffusely positive staining for C4d.


Pure AMR is relatively uncommon in ABO-compatible grafts - it should be diagnosed on the basis of strict criteria and requires treatment with antibody-depleting immunosuppression. C4d immunostaining in isolation has limited diagnostic value. However, the presence of diffuse C4d immunostaining (involving endothelium or stroma in >50% of portal tracts or sinusoids) suggests a significant component of antibody-mediated graft damage. In a person with suggestive histological features, this finding should prompt testing for DSAs. Even in the absence of typical histological features of AMR, the combined presence of DSAs and diffuse C4d positivity is associated with more frequent or severe acute and chronic rejection, which may also warrant treatment with antibody-depleting immunosuppression.

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