In April 2002, the FDA approved the Cylex Immune Cell Function Assay (Cylex Inc., Columbia, MD) for the detection of cell mediated immune response in populations undergoing immunosuppressive therapy for organ transplant. FDA clearance of tests does not include specific indications. The test calculates the concentration of ATP (ng/ml) from a calibration curve and compared to ATP level ranges to characterize the cellular immune function of the sample. A variety of studies since 2009 have reached conflicting and contradictory conclusions regarding the utility of this test in liver, heart and kidney transplantation. Some showed no efficacy and others had promising but inconclusive results and recommend farther study. The American Society of Transplantation (AST) does not mention the use of the Cylex Immune Cell Function assay in its recommendations for the screening, monitoring and reporting of infections complications in the evaluation of recipients of organ transplantation (AST, 2006). Chon and Brennan (2009) commented that there is no consensus on the utility of the Immuknow assay in renal transplant rejection other than in the research setting. Martinu et al (2009) commented that “the data in lung transplantation are scarce and not very promising to date”, and that “the ImmuKnow assay does not seem to have the potential to differentiate between infection and rejection in lung transplant recipients and, until more data becomes available, should not be used clinically in this patient population.”
More recent studies continue to exhibit the same pattern. Torio et al (2011) stated that the Cylex ImmuKnow assay provides a rapid assessment of global immune function in immunocompromised patients by measuring the global immune responses of CD4 T cells from a whole-blood sample. The authors concluded that these findings confirmed that the ImmuKnow assay identified transplant patients at risk for infection. It may provide information to guide immunosuppressive therapy, but the assay did not seem to have the potential to differentiate subjects experiencing rejection.
De Paolis et al (2011) concluded that this preliminary analysis showed a beneficial capacity of this assay to represent the global depression of the immune system. They did not confirm the predictive value of higher IK values for an increased risk of an acute rejection episode.
Huskey et al (2011) retrospectively analyzed 1,330 ImmuKnow assay values in 583 renal transplant recipients at a single center from 2004 to 2009 and correlated these values with episodes of opportunistic infections (OI) and acute rejection (AR) in the subsequent 90 days. The authors concluded that these findings fail to show an association between single time point ImmuKnow assay values and the subsequent development of an adverse event in the subsequent 90 days. The optimal use of the ImmuKnow assay in kidney transplantation has yet to be determined. A number of other studies reached similar conclusions.
This test is not currently recommended by any guidelines and should be considered investigational at this time.
Clinical / Medical References:
- Chon WJ, Brennan DC. Investigational methods in the diagnosis of acute renal allograft rejection. UpToDate [online serial]. Waltham, MA: UpToDate; October 2009.
- Martinu T, Chen DF, Palmer SM. Acute rejection and humoral sensitization in lung transplant recipients. Proc Am Thorac Soc. 2009;6(1):54-65.
- Torío A, Fernández E, Montes-Ares O, et al. Lack of association of immune cell function test with rejection in kidney transplantation. Transplant Proc. 2011;43(6):2168-2170.
- De Paolis P, Favarò A, Piola A, et al. “Immuknow” to measurement of cell-mediated immunity in renal transplant recipients undergoing short-term evaluation. Transplant Proc. 2011;43(4):1013-1016.
- Huskey J, Gralla J, Wiseman AC. Single time point immune function assay (ImmuKnow) testing does not aid in the prediction of future opportunistic infections or acute rejection. Clin J Am Soc Nephrol. 2011;6(2):423-429.
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