A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells is associated with acute hepatic rejection: a case control study.

ABSTRACT

BACKGROUND: T 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. METHODS: Blood 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. RESULTS: Upon activation the expression of TGF-ß 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). CONCLUSIONS: A 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.