Background: Dosage of immunosuppressive drugs in transplant patients must be balanced to prevent graft rejection and infectious complications. Knowledge on general immune function may therefore help to assess over- or underimmunosuppression. We therefore characterized cellular immune function among transplant patients and controls after polyclonal stimulation of blood samples with the QuantiFERON Monitor assay (Qiagen). Susceptibility towards immunosuppressive drugs and their dosages was assessed in vitro and in vivo. Moreover, longitudinal analysis before and after transplantation was assessed as tool to predict infection or rejection episodes.

Methods: 46 controls, 68 dialysis patients, and 68 transplant patients were recruited cross-sectionally and longitudinally. Samples were stimulated for 20h and IFNγ secretion was measured by ELISA. Intracellular staining of IFNγ, TNFα, IL2, and IL17 was performed among T-, B-, and NK cells using flow-cytometry. Infection and rejection episodes were collected from clinical records.

Results: Cytokine secretion was mainly observed in CD4, CD8 and NK cells, and IFNγ was the dominant cytokine. In general, intra-assay variability of cell-reactivity was low (CV=10.4±6.2%), whereas inter-assay variability from longitudinal analyses was rather high despite absence of clinical events (CV=65.0±35.7%). Cyclosporine, tacrolimus and steroids applied in vitro dose-dependently reduced IFNγ secretion (by 66.6%, 57.2% and 68.5%, respectively), and reactivity was further reduced when calcineurin inhibitors were combined with steroids (by 80.5% for cyclosporine, by 85.0% for tacrolimus). As expected, IFNγ levels significantly differed between controls, dialysis patients, and transplant patients with lowest levels in the latter (p<0.001). Among transplant patients tested before and after transplantation, lowest IFNγ levels were observed in the early period after transplantation. Nevertheless, test results did not differ in patients with and without subsequent infection or rejection episodes (p=n.s.).

Conclusion: Cell-reactivity after polyclonal stimulation is dose-dependently inhibited by immunosuppressive drugs. The assay may have potential for assessing loss of general immunocompetence and for pharmacodynamic monitoring of immunosuppressive drugs in transplant patients, but does not seem to predict infection or rejection episodes on an individual basis.

CITATION INFORMATION: Marx S., Adam C., Leyking S., Sester U., Sester M. Polyclonal Cellular Immune Function is Dose-Dependently Inhibited by Immunosuppressive Drugs but Has Limited Value in Predicting Infection or Rejection Episodes Am J Transplant. 2017;17 (suppl 3).

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