title: The fractional excretion of soluble interleukin-2 receptor-alpha is an excellent predictor of the interleukin-2 receptor-alpha status after treatment with daclizumab.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Nijmegen, The Netherlands. c.termeulen@nier.umcn.nl
authors.forename: Cornelis G
authors.initials: CG
authors.lastname: ter Meulen
authors.forename: Cor W M
authors.initials: CW
authors.lastname: Jacobs
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
authors.forename: Ina S
authors.initials: IS
authors.lastname: Klasen
authors.forename: Luuk B
authors.initials: LB
authors.lastname: Hilbrands
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Hoitsma
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood / Q000652:urine; D017252:CD3 Complex / Q000097:blood; D000077561:Daclizumab; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D011237:Predictive Value of Tests; D018123:Receptors, Interleukin / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D017252:CD3 Complex; C508017:IL2RA protein, human; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin; D000077561:Daclizumab; D016650:Fluorescein-5-isothiocyanate