BACKGROUND: Current monitoring systems of immunosuppression in solid-organ transplant recipients are typically focused on prevention of clinical toxicities of immunosuppressive drugs. Unfortunately, these strategies are often not tailored to the individual and do not determine the optimal level of immunosuppression for these patients. Recently, the Cylex Immune Cell Function Assay (ImmuKnow; Cylex, Inc., Columbia, MD) was approved by the U.S. Food and Drug Administration (FDA) to measure global immune response in solid-organ transplant patients receiving immunosuppressive therapy. We sought to identify the level of functional immunity as measured by the ImmuKnow assay in lung transplant recipients and to correlate these values with the dose and trough levels of immunosuppression as well as other clinical parameters in lung transplant recipients. METHODS: We assessed the functional immune response by the ImmuKnow assay in 143 sequential blood samples from 57 lung transplant recipients from Loyola University Medical Center. RESULTS: The average ImmuKnow assay in stable lung transplant recipients was 244 +/- 138 adenosine triphosphate (ATP) ng/ml and the median level was 236 ATP ng/ml (range 5 to 669 ATP ng/ml), approximately 703 +/- 695 days after lung transplantation. There was no correlation between ImmuKnow levels and tacrolimus trough levels. Stepwise multiple regression analysis identified African American race as an independent predictor of ImmuKnow assay levels when age, gender and underlying diagnosis were taken into account (p < 0.04). Fifteen infected lung transplant recipients had a lower ImmuKnow level at the time of their infections as compared with stable lung transplant recipients (111 +/- 83 vs 283 +/- 143 ATP ng/ml, respectively, p = 0.0001). Sixteen of the remaining 42 patients had low ImmuKnow assay values (<225 ATP ng/ml), but did not have active infection. There were only 2 patients with acute rejection of Grade A1 in this cohort. There were no identifiable associations of the ImmuKnow level with either acute rejection episode. CONCLUSIONS: The Cylex ImmuKnow assay levels were lower in infected lung transplant recipients compared with non-infected recipients and increased with treatment of these infections. It remains unclear whether the ImmuKnow assay reflects over-immunosuppressed individuals at risk of infection or bone marrow suppression by infectious agents. Further investigation will determine the role of the ImmuKnow assay in tailoring immunosuppression in lung transplant recipients.
BACKGROUND: Current monitoring systems of immunosuppression in solid-organ transplant recipients are typically focused on prevention of clinical toxicities of immunosuppressive drugs. Unfortunately, these strategies are often not tailored to the individual and do not determine the optimal level of immunosuppression for these patients. Recently, the Cylex Immune Cell Function Assay (ImmuKnow; Cylex, Inc., Columbia, MD) was approved by the U.S. Food and Drug Administration (FDA) to measure global immune response in solid-organ transplant patients receiving immunosuppressive therapy. We sought to identify the level of functional immunity as measured by the ImmuKnow assay in lung transplant recipients and to correlate these values with the dose and trough levels of immunosuppression as well as other clinical parameters in lung transplant recipients. METHODS: We assessed the functional immune response by the ImmuKnow assay in 143 sequential blood samples from 57 lung transplant recipients from Loyola University Medical Center. RESULTS: The average ImmuKnow assay in stable lung transplant recipients was 244 +/- 138 adenosine triphosphate (ATP) ng/ml and the median level was 236 ATP ng/ml (range 5 to 669 ATP ng/ml), approximately 703 +/- 695 days after lung transplantation. There was no correlation between ImmuKnow levels and tacrolimus trough levels. Stepwise multiple regression analysis identified African American race as an independent predictor of ImmuKnow assay levels when age, gender and underlying diagnosis were taken into account (p < 0.04). Fifteen infected lung transplant recipients had a lower ImmuKnow level at the time of their infections as compared with stable lung transplant recipients (111 +/- 83 vs 283 +/- 143 ATP ng/ml, respectively, p = 0.0001). Sixteen of the remaining 42 patients had low ImmuKnow assay values (<225 ATP ng/ml), but did not have active infection. There were only 2 patients with acute rejection of Grade A1 in this cohort. There were no identifiable associations of the ImmuKnow level with either acute rejection episode. CONCLUSIONS: The Cylex ImmuKnow assay levels were lower in infected lung transplant recipients compared with non-infected recipients and increased with treatment of these infections. It remains unclear whether the ImmuKnow assay reflects over-immunosuppressed individuals at risk of infection or bone marrow suppression by infectious agents. Further investigation will determine the role of the ImmuKnow assay in tailoring immunosuppression in lung transplant recipients.
Authors: Joshua A Blatter; Stuart C Sweet; Carol Conrad; Lara A Danziger-Isakov; Albert Faro; Samuel B Goldfarb; Don Hayes; Ernestina Melicoff; Marc Schecter; Gregory Storch; Gary A Visner; Nikki M Williams; David Wang Journal: Pediatr Transplant Date: 2017-10-29
Authors: John R Greenland; Tiffany Chong; Angelia S Wang; Emily Martinez; Pavan Shrestha; Jasleen Kukreja; Steven R Hays; Jeffrey A Golden; Jonathan P Singer; Qizhi Tang Journal: Am J Transplant Date: 2018-05-22 Impact factor: 8.086
Authors: Michael Y Shino; S Samuel Weigt; Rajan Saggar; David Elashoff; Ariss Derhovanessian; Aric L Gregson; Rajeev Saggar; Elaine F Reed; Bernard M Kubak; Joseph P Lynch; John A Belperio; Abbas Ardehali; David J Ross Journal: J Heart Lung Transplant Date: 2012-09 Impact factor: 10.247
Authors: Camila Macedo; Adriana Zeevi; Carol Bentlejewski; Iulia Popescu; Michael Green; David Rowe; Louise Smith; Steve Webber; Diana Metes Journal: Transplantation Date: 2009-07-15 Impact factor: 4.939