The fractional excretion of soluble interleukin-2 receptor-alpha is an excellent predictor of the interleukin-2 receptor-alpha status after treatment with daclizumab

BACKGROUND: Daclizumab is a humanized monoclonal antibody against the alpha-chain of the interleukin (IL)-2 receptor (R). The authors previously have shown that the urinary excretion of soluble (s) IL-2Ralpha is dependent on the presence of daclizumab in serum. The authors investigated whether the IL-2Ralpha status, as assessed by flow cytometric analysis, is reflected by the concentration of sIL-2Ralpha in the urine and serum. METHODS: Two hundred seventy-two measurements were performed in 46 renal transplant recipients who were treated with daclizumab in combination with tacrolimus and mycophenolate mofetil. Soluble IL-2Ralpha was measured in urine and serum with Immulite IL-2R, a solid-phase enzyme-linked immunosorbent assay. Complete blockade of the IL-2Ralpha was defined as the presence of less than 5% IL-2Ralpha+ lymphocytes in the CD3+ population. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of serum and urine sIL-2Ralpha in predicting IL-2Ralpha blockade. RESULTS: The calculated fractional excretion of sIL-2Ralpha proved to be an excellent predictor of the blockade of IL-2Ralpha (ROC analysis area under the curve, 0.95+/-0.01). A calculated fractional excretion of sIL-2Ralpha lower than 0.5% had a specificity of 100% and a sensitivity of 75% for the assessment of blockade of IL-2Ralpha. CONCLUSIONS: Blockade of IL-2Ralpha after treatment with daclizumab can reliably be assessed by calculation of the fractional excretion of sIL-2Ralpha. This method is easier to use compared with flow cytometric analysis of IL-2Ralpha+ lymphocytes.