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-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). 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.

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Granzyme B–Producing B Cells Function as a Feedback Loop for T Helper Cells in Liver Transplant Recipients with Acute Rejection

Inflammation ◽

10.1007/s10753-021-01498-9 ◽

2021 ◽

Author(s):

Wen-Li Xu ◽

Ruo-lin Wang ◽

Zhe Liu ◽

Qiao Wu ◽

Xian-Liang Li ◽

...

Keyword(s):

B Cells ◽

Acute Rejection ◽

Liver Transplant ◽

T Helper Cells ◽

Feedback Loop ◽

Granzyme B ◽

Transplant Recipients ◽

T Helper ◽

Helper Cells ◽

Liver Transplant Recipients

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Intracellular IFN-γ and IL-2 expression monitoring as surrogate markers of the risk of acute rejection and personal drug response in de novo liver transplant recipients

Cytokine ◽

10.1016/j.cyto.2012.10.026 ◽

2013 ◽

Vol 61 (2) ◽

pp. 556-564 ◽

Cited By ~ 51

Author(s):

O. Millán ◽

L. Rafael-Valdivia ◽

E. Torrademé ◽

A. López ◽

V. Fortuna ◽

...

Keyword(s):

Acute Rejection ◽

Liver Transplant ◽

Drug Response ◽

De Novo ◽

Surrogate Markers ◽

Transplant Recipients ◽

Ifn Γ ◽

Liver Transplant Recipients

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A Rise in Percentages of Circulating Lymphocyte Subsets Correlates With Acute Rejection in Liver Transplant Recipients

10.21203/rs.3.rs-139859/v1 ◽

2021 ◽

Author(s):

Fei Pan ◽

Shuang Cao ◽

Xian-Liang Li ◽

Wen-Li Xu ◽

Han Li ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Acute Rejection ◽

Liver Transplant ◽

Nk Cells ◽

Lymphocyte Subsets ◽

T Cell Subsets ◽

Transplant Recipients ◽

Nk T Cells ◽

Liver Transplant Recipients

Abstract Background: Little is known about the shift of circulating lymphocyte subsets following liver transplantation and thus, its relationship with acute rejection. Methods: Liver transplant recipients were enrolled to assess the effect of primary liver diseases, gender, age, and follow-up periods on the shift of circulating lymphocyte subsets. Moreover, patients with rejection were paired to assess the effect of the shift on rejection.Results: When compared with patients from the middle-term group (29-180 d) and the long-term group (>180 d), patients from the short-term group (< 29 d) had the lowest absolute counts of T cell subsets, NK cells and NK T cells, and the lowest percentages of T cell subsets, B cells, NK cells and NK T cells but the highest percentage of DC. However, other factors did not affect circulating lymphocyte subsets. Percentages of T cells, CD4+T cells, B cells and NK T cells were higher in patients with acute rejection while percentages of T cell subsets and NK cells decreased after anti-rejection treatment. The percentage of NK T cells was identified to be the only independent predictor for acute rejection. The predicted probability was calculated using binary logistic with the area under the curve of 0.89, which had a sensitivity of 70.6% and a specificity of 94.1% at a cut-off value of 0.69.Conclusions: Circulating lymphocyte subsets gained a global recovery over the post-transplant period, leading to a sharp rise in percentages of circulating lymphocyte subsets, which was in close relation to the occurrence of acute rejection.

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Activated CD4+ T‐cells and highly differentiated alloreactive CD4+ T‐cells distinguish operationally tolerant liver transplant recipients

Liver Transplantation ◽

10.1002/lt.26188 ◽

2021 ◽

Author(s):

Aafke A. Duizendstra ◽

Robert J. Knegt ◽

Shanta Mancham ◽

Mariska Klepper ◽

Dave L. Roelen ◽

...

Keyword(s):

T Cells ◽

Liver Transplant ◽

Cd4 T Cells ◽

Transplant Recipients ◽

Liver Transplant Recipients

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Comparison of Three Cellular Assays to Predict the Course of CMV Infection in Liver Transplant Recipients

Vaccines ◽

10.3390/vaccines9020088 ◽

2021 ◽

Vol 9 (2) ◽

pp. 88

Author(s):

Smaranda Gliga ◽

Melanie Fiedler ◽

Theresa Dornieden ◽

Anne Achterfeld ◽

Andreas Paul ◽

...

Keyword(s):

Liver Transplant ◽

Solid Organ Transplantation ◽

Solid Organ ◽

Transplant Recipients ◽

Cmv Infection ◽

Cellular Assays ◽

Risk Patients ◽

Ifn Γ ◽

Liver Transplant Recipients

To estimate protection from cytomegalovirus (CMV) replication after solid organ transplantation, CMV serology has been considered insufficient and thus CMV immunity is increasingly assessed by cellular in vitro methods. We compared two commercially available IFN-γ ELISpot assays (T-Track CMV and T-SPOT.CMV) and an IFN-γ ELISA (QuantiFERON-CMV). Currently, there is no study comparing these three assays. The assays were performed in 56 liver transplant recipients at the end of antiviral prophylaxis and one month thereafter. In CMV high- or intermediate-risk patients the two ELISpot assays showed significant correlation (p < 0.0001, r > 0.6) but the correlation of the ELISpot assays with QuantiFERON-CMV was weaker. Results of both ELISpot assays were similarly predictive of protection from CMV-DNAemia ≥500 copies/mL [CMV pp65 T-SPOT.CMV at the end of prophylaxis: area under curve (AUC) = 0.744, cut-off 142 spot forming units (SFU), sensitivity set to 100%, specificity 46%; CMV IE-1 T-Track CMV at month 1: AUC = 0.762, cut-off 3.5 SFU, sensitivity set to 100%, specificity 59%]. The QuantiFERON-CMV assay was inferior, reaching a specificity of 23% when setting the sensitivity to 100%. In conclusion, both CMV-specific ELISpot assays appear suitable to assess protection from CMV infection/reactivation in liver transplant recipients.

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