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

• Published in: Transplantation Vol. 77; no. 2; pp. 281 - 286
• Main Authors: TER MEULEN, Cornelis G, JACOBS, Cor W. M, WETZELS, Jack F. M, KLASEN, Ina S, HILBRANDS, Luuk B, HOITSMA, Andries J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 27-01-2004
• Subjects: Adult; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Biological and medical sciences; Biomarkers - blood; Biomarkers - urine; CD3 Complex - blood; Combined surgery. Multiple transplantations; Female; Flow Cytometry; Fluorescein-5-isothiocyanate; Graft Rejection - epidemiology; Humans; Immunoglobulin G - therapeutic use; Immunosuppressive Agents - therapeutic use; Interleukin-2 Receptor alpha Subunit; Kidney Transplantation - immunology; Male; Medical sciences; Predictive Value of Tests; Receptors, Interleukin - blood; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Treatment Outcome; Excretion; Predictor; Cytokine; Transplantation; Soluble form; Daclizumab; Treatment; Interleukin 2; Surgery; Graft; Immunosuppressive agent; Predictive factor; Biological receptor
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/01.TP.0000101702.73759.F3

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.
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.
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.
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.