Department of Hepatobiliary and Pancreaticosplenic Surgery, Medical Research Center, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongtinan Road, Chaoyang District, Beijing, 100020, China.
J Transl Med. 2021 May 1;19(1):187. doi: 10.1186/s12967-021-02855-w.
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.
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.
Upon activation the expression of TGF-β and granzyme B in CD19B cells, and the expression of IL-2 and IFN-γ in CD4T cells were higher in acute hepatic rejection. However, only the frequencies of granzyme BCD19B cells and IFN-γCD4T 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).
A combination of the percentages of IFN-γCD4T cells and granzyme BCD19B cells can distinguish rejection from non-rejection, which can be used as a potential prognostic marker for acute rejection in liver transplant recipients.
T 细胞和 B 细胞在同种免疫反应中发挥关键作用。本研究旨在描述急性肝排斥反应过程中 T 细胞亚群和 B 细胞亚群的变化,并进一步确定它们是否可作为预后标志物。
收集和分析肝移植受者伴有和不伴有急性肝排斥反应以及验证队列的血液样本和临床数据。
在急性肝排斥反应中,CD19B 细胞中 TGF-β 和颗粒酶 B 的表达、CD4T 细胞中 IL-2 和 IFN-γ 的表达上调。然而,只有颗粒酶 BCD19B 细胞和 IFN-γCD4T 细胞的频率与肝功能以及彼此相关。这两个细胞亚群的组合作为一种新的标志物可以区分排斥与非排斥(曲线下面积 0.811,p=0.001),截断值为 62.93%,对更严重的组织学变化更敏感(p=0.027)。此外,新型标志物>62.93%的组中急性排斥反应的发生率更高(p=0.000)。在验证队列中进一步证实了新型标志物的作用,该标志物被确定为急性排斥的唯一显著独立危险因素(优势比:0.923;95%置信区间:0.885-0.964;p=0.000)。
IFN-γCD4T 细胞和颗粒酶 BCD19B 细胞的百分比相结合可以区分排斥与非排斥,可作为肝移植受者急性排斥的潜在预后标志物。