Abstract
BackgroundAs it is often difficult for a transplant pathologist to make a definite diagnosis of acute cellular rejection (ACR) by routine morphological analysis of liver allograft biopsy, supplementary methods and objective markers are needed to facilitate this determination.MethodsTo evaluate the diagnostic value of cytotoxic molecules in ACR episodes, immunohistochemical staining for perforin, granzyme B and T-cell intracellular antigen-1 (TIA-1) were performed in liver allograft biopsies. The positive cells in the portal tract area and lobules were counted separately to investigate the distribution of the cytotoxic molecules.ResultsThe immunohistochemical study showed that the overall positive rates for the three markers were not significantly different between the ACR and non-ACR groups. However, in the portal tract area, perforin-, granzyme B- and TIA-1-positive cells in the ACR group were significantly more than those in the non-ACR groups. In the lobules, perforin- and granzyme B-positive cells in the ACR group were significantly more than those in the biliary complication and opportunistic infection groups, while TIA-1-positive cells was significantly fewer than those in non-ACR groups. The numbers of positive cells in the portal tract area correlated with the rejection activity index of ACR.ConclusionsThese results indicate that, though the overall positive rates have nonsense in ACR diagnosis, the quantification and local distribution analysis of cytotoxic molecule positive cells in liver tissue is helpful for differential diagnosis and severity evaluation of ACR following liver transplantation.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2292255038100487
Highlights
With the incidence reportedly ranging from 30% to 70%, acute cellular rejection (ACR) is one of the most common complications after orthotopic liver transplantation (OLT) [1,2]
Histological observation In the 108 cases, 62 cases were diagnosed as ACR and 46 were non-ACR, including 19 biliary complications (BC), 6 ischemic/reperfusion injuries (I/R), 6 opportunistic infections (OI) and 15 undefined complications (UD)
The expression and distribution of cytotoxic effector molecules in ACR and non-ACR tissue Perforin, granzyme B and Tcell intracellular antigen-1 (TIA-1) were mainly located in the cytoplasm of inflammatory cells in portal tracts and lobules, and they were frequently observed in the epithelia of interlobular bile ducts and subendothelial portions of portal veins in ACR, (Figure 2 and 3)
Summary
With the incidence reportedly ranging from 30% to 70%, acute cellular rejection (ACR) is one of the most common complications after orthotopic liver transplantation (OLT) [1,2]. It is generally accepted that T cell-mediated immune reactions play a pivotal role in the pathogenesis of ACR, and CD8+ cytotoxic T cells induce target cell death during acute allograft rejection in liver allograft tissues [6,7,8] Cytotoxic molecules such as perforin, granzyme B and Tcell intracellular antigen-1 (TIA-1) are present in the cytoplasmic granules of cytotoxic T cells and function at the effector end of the acute rejection process [9]. The diagnostic value of these cytotoxic molecules in acute cellular rejection after liver transplantation has not yet been clearly elucidated As it is often difficult for a transplant pathologist to make a definite diagnosis of acute cellular rejection (ACR) by routine morphological analysis of liver allograft biopsy, supplementary methods and objective markers are needed to facilitate this determination
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