ImmuKnow as a diagnostic tool for predicting infection and acute rejection in adult liver transplant recipients: A systematic review and meta-analysis

Abstract

Immune status monitoring of transplant recipients could identify patients at risk of acute rejection, infection, and cancer, which are important sources of morbidity and mortality in these patients. The ImmuKnow assay provides an objective assessment of the cellular immune function of immunosuppressed patients. Inconclusive results concerning the ability of the ImmuKnow test to predict acute rejection and infection have raised concerns about the predictive value of ImmuKnow in liver transplant recipients. We conducted a systematic literature review to identify studies published up to March 2012 that documented the use of ImmuKnow for monitoring immune function in liver transplant recipients. The study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 score. We identified 5 studies analyzing ImmuKnow performance for infection and 5 studies analyzing ImmuKnow performance for acute rejection. The pooled sensitivity, specificity, positive likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 83.8% [95% confidence interval (CI) ¼ 78.5%-88.3%], 75.3% (95% CI ¼ 70.9%-79.4%), 3.3 (95% CI ¼ 2.8-4.0), 14.6 (95% CI ¼ 9.6-22.3), and 0.824 6 0.034, respectively, for infection and 65.6% (95% CI ¼ 55.0%-75.1%), 80.4% (95% CI ¼ 76.4%-83.9%), 3.4 (95% CI ¼ 2.4-4.7), 8.8 (95% CI ¼ 3.1-24.8), and 0.835 6 0.060, respectively, for acute rejection. Heterogeneity was low for infection studies and high for acute rejection studies. In conclusion, the ImmuKnow test is a valid tool for determining the risk of further infection in adult liver transplant recipients. Significant heterogeneity across studies precludes the conclusion that ImmuKnow identifies liver transplant patients at risk for rejection. Liver Transpl 18:1245-1253, 2012. V C 2012 AASLD.Received April 18, 2012; accepted June 16, 2012.In the field of solid organ transplantation, the maintenance of an adequate level of immunosuppression is of the greatest importance. On the one hand, overimmunosuppression can promote the appearance of infection, cancer, and other undesirable secondary effects. Infectious diseases remain an important source of morbidity and mortality for all types of transplant patients. 1 Up to two-thirds of all liver Abbreviations: AUC, area under the curve; AUC-ROC, area under the receiver operating characteristic curve; CI, confidence interval; df, degrees of freedom; DOR, diagnostic odds ratio; HCV, hepatitis C virus; iATP, intracellular adenosine triphosphate; QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies 2; SE, standard error; SROC, summary receiver operating characteristic.

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

“…A meta-analysis that summarized eight studies comprising over 1 700 patients reported a sensitivity and specificity of 58% and 69%, respectively [16]. These pooled estimates were slightly better in a second meta-analysis restricted to liver transplant recipients [17]. In addition to the originally intended role of the ImmuKnow â assay as an instrument to analyze the efficiency of post-transplant immunosuppressive regimen, it is assumed that the production of iATP by PHA-stimulated CD4 + T cells recapitulates the functional responsiveness of the cell-mediated response [2,9].…”

“…Cumulative incidence curves were constructed for study outcomes (overall and bacterial infection and CMV diseases) with death treated as a competing risk, and differences between groups were compared with the log-rank test. Uni-and multivariate Cox regression models were used to evaluate the association between iATP categories at each point (baseline and months 1 and 6 after transplantation) and outcomes throughout the following periods (early [first month], intermediate [months [1][2][3][4][5][6], and late periods [months [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24], respectively) [1]. Associations were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs).…”

“…A detailed description of the 13 cases of CMV disease diagnosed in the intermediate period in which iATP levels at month 1 were available is provided as Supporting Information (Table S2). Finally, there were no significant differences in the incidence of infection at the end of the late period (i.e., months [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] according to the CMI response at month 6.…”

“…Lastly, the protocol of the ImmuKnow â assay is relatively simple and does not require special laboratory equipment. Notwithstanding these advantages and the large number of studies performed [11][12][13][14][15], the clinical application of this biomarker is not widespread, likely due to the suboptimal performance shown by the ImmuKnow â assay for predicting post-transplant infection [16,17]. A shortcoming of most studies is that the indication for measuring iATP was motivated by the clinical suspicion of infection rather than being ordered within a scheduled monitoring strategy.…”

High-dose immunosuppressant alters the immunological status of New Zealand white rabbits following skin transplantation

“…Fluorescence-based flow cytometry is advantageous for use as a functional assay for specific cytotoxic T lymphocytes (CTLs) (24,25), as it improves on the sensitivity and specificity of in vitro CTL techniques. Fluorescence-based flow cytometry is safe for use in clinical and laboratory experiments and avoids radioactive contamination during experimentation.…”