Monitoring of intracellular adenosine triphosphate in CD4⁺T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients

Abstract

SUMMARYThe measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4 + T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; Pvalue = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients.

Epidemiology, risk factors, and outcomes associated with cytomegalovirus in adult kidney transplant recipients: A systematic literature review of real‐world evidence

“…An additional eight studies meeting inclusion criteria were identified from the manual review of bibliographies of published SLRs. Ultimately, 86 5,6,14‐97 citations representing 81 unique studies 5,6,14‐92 including 69 803 participants met the inclusion criteria.…”

Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the “Net State of Immunosuppression”

“…In 248 liver recipients, low iATP was associated with invasive fungal infection, but not bacterial infection [64]. In 100 kidney recipients, lower iATP was associated with CMV disease, but not bacterial infections [65]. Metaanalyses of iATP studies found discordant results [66][67][68].…”

Immune function as predictor of infectious complications and clinical outcome in patients undergoing solid organ transplantation (the ImmuneMo:SOT study): a prospective non-interventional observational trial

“…The principle of the test is measuring intracellular adenosine triphosphate (ATP) production in CD4 + -cells upon whole blood stimulation with phytohemagglutinin (PHA) [15]. Although the technique is promising, many of the studies conducted with ImmuKnow® have limitations including retrospective design, small number of recipients, single measurement and/or low follow-up time, and results so far are conflicting [12–14, 16–23]. One promising randomized controlled study by Ravaioli et al found that immunosuppression dosed according to results of serial testing with ImmuKnow® increased 1-year patient survival and lowered the incidence of infections in liver transplant patients [11].…”

“…The use of functional assays to determine immune function has gained attention as a possible tool to improve dosage of immunosuppression in SOT recipients [10–23]. Previously, functional assays have been expensive and required high level of technical skills and hands-on time in the laboratory, limiting the utility of this approach.…”