Abstract
BackgroundT cells and B cells play a key role in alloimmune responses. We aimed to characterize the shift of T cell subsets and B cell subsets during acute hepatic rejection, and further determine whether they could serve as a prognostic marker.MethodsBlood samples together with the clinical data from liver transplant recipients with and without acute hepatic rejection were collected and analyzed as well as from a validation cohort.ResultsUpon activation the expression of TGF-β and granzyme B in CD19+B cells, and the expression of IL-2 and IFN-γ in CD4+T cells were higher in acute hepatic rejection. However, only the frequencies of granzyme B+CD19+B cells and IFN-γ+CD4+T cells correlated with liver function in addition to with each other. A combination of the two cell subsets as a novel marker could classify rejection versus non-rejection (area under the curve 0.811, p = 0.001) with the cut-off value of 62.93%, which was more sensitive for worse histological changes (p = 0.027). Moreover, the occurrence rate of acute rejection was higher in the group with the novel marker > 62.93% (p = 0.000). The role of the novel marker was further confirmed in a validation cohort, which was identified to be the only significant independent risk factor for acute rejection (odds ratio: 0.923; 95% CI confidence interval: 0.885–0.964; p = 0.000).ConclusionsA combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells can distinguish rejection from non-rejection, which can be used as a potential prognostic marker for acute rejection in liver transplant recipients.
Highlights
Liver transplantation is a major therapeutic approach in patients with end-stage liver diseases [1]
In this study, we found that a combination of percentages of activated IFN-γ+CD4+T cells and activated Granzyme B (GrB)+CD19+B cells can distinguish rejection from nonrejection, which can be used as a novel biomarker for diagnosis of acute rejection in liver transplant recipients (LTR)
IL-17 is a pro-inflammatory cytokine implicated in the pathogenesis of lung and renal transplantation as reduced IL-17 production was associated with attenuation of acute rejection [21, 22]
Summary
Liver transplantation is a major therapeutic approach in patients with end-stage liver diseases [1]. Following transplantation acute rejection remains a major challenge despite the development of immunosuppressive drugs [2]. Abnormalities in liver function may raise concerns about acute rejection, invasive liver biopsies are still the gold standard for definitive diagnoses [3]. A potential biomarker with minimal invasion for the diagnosis of acute rejection after liver transplantation has. Acute rejection is realized via the immune cells, blood-derived biomarkers are under intensive research. By means of producing different cytokines and exerting different biological functions, C D4+T cells are thought to play a crucial role during the rejection process [4, 5]. Immature dendritic cells-derived exosomes improved the percent of survival and suppressed rejection associated cytokines IFN-γ, IL-2, IL-17 production [9]. We aimed to characterize the shift of T cell subsets and B cell subsets during acute hepatic rejection, and further determine whether they could serve as a prog‐ nostic marker
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