Immune Response following Liver Transplantation Compared to Kidney Transplantation: Usefulness of Monitoring Peripheral Blood CD4+ Adenosine Triphosphate Activity and Cytochrome P450 3A5 Genotype Assay

Abstract

Seventy living donor liver transplantation (LDLT) and 39 kidney transplantation (KT) patients were randomly screened by using the peripheral blood CD4+ adenosine triphosphate activity (ATP) assay (IMK assay). The patients were divided into 2 groups in each organ transplantation with low IMK ATP level (<225 ng/mL) or high (>225) (LT-L: n = 23, KT-L: n = 19, LT-H: n = 47, and KT-H: n = 20, resp.). The incidence of bacterial and/or viral infection was significantly higher in LT-L group than in LT-H group (74.0 versus 8.5%: P < 0.001). Occurrence of total viral infection in KT-L was also significantly higher than that in KT-H (36.8 versus 10%: P = 0.046). The sensitivity and specificity of the IMK assay for identifying risk of infection was 0.810 and 0.878 in LDLT patients and 0.727 and 0.607 in KT patients. The percentage of LDLT patients with cytochrome P450 3A5 (CYP3A5) *1/*1 or *1/*3 genotype (expressors) was significantly higher in LT-L group than in LT-H group (53.8 versus 20.7%: P = 0.032). In both LDLT and KT patients, the IMK assay can be useful for monitoring immunological aspects of bacterial and/or viral infection. CYP3A5 expressors in LT-L group are related to postoperative infections.

Monitoring of peripheral blood cluster of differentiation 4+ adenosine triphosphate activity and CYP3A5 genotype to determine the pharmacokinetics, clinical effects and complications of tacrolimus in patients with autoimmune diseases

“…in 2002, monitors the function of cluster of differentiation (CD) 4 + T cells by measuring the intracellular concentration of adenosine triphosphate (ATP) (8). The IMK assay has previously been used to identify transplant patients at risk of infection (patients with low IMK ATP levels: <225 ng/ml) or rejection (patients with high IMK ATP (1,2,9). However, it has been argued that the IMK assay is not a useful indicator of infection or rejection risk (3,4), and for patients with autoimmune diseases, the efficacy of the IMK assay in monitoring immunological aspects remains unclear.…”

Monitoring of blood immunosuppressant concentrations and lymphocyte activation for predicting viral infections following kidney transplantation: A pilot study

“…It is well established that the CYP3A5 genotype is associated with variability in blood tacrolimus concentrations, and the authors have also reported correlations between genetic polymorphisms and blood tacrolimus levels in individuals who have undergone kidney, liver, or hematopoietic stem cell transplantation. [24][25][26] The patient who experienced acute rejection was found to have the CYP3A5 1/*3 genotype, which is not generally associated with markedly elevated blood tacrolimus levels. However, there were no appreciable changes in the AUC of mycophenolic acid, inhibition of the IL-2 receptor by basiliximab in CD4 + T cells, or the expression levels of IL-2 and IFN-γ in effector T cells.…”

Monitoring T cell alloreactivity

“…However, these studies measured the ImmuKnow values at the time of disease rather than before its onset, which prevented any analysis on the predictive value of the assay. Other investigators tried to address this issue and reported that low ImmuKnow values are associated with an increased incidence of infections in stable transplant recipients on maintenance immunosuppression [89, 92–95]. Yet, these studies were small with relatively few infection episodes and short follow-up periods.…”