Decreased renal excretion of soluble interleukin-2 receptor α after treatment with daclizumab

Decreased renal excretion of soluble interleukin-2 receptor α after treatment with daclizumab.BackgroundDaclizumab (±150 kD), a humanized monoclonal antibody (mAb) against the alpha-chain of the membrane-bound interleukin-2 (IL-2) receptor (IL-2R) also binds soluble interleukin-2R α (sIL-2Rα; ±45 kD), and thus may influence the glomerular filtration of sIL-2Rα.MethodsWe have studied the influence of daclizumab on the renal excretion of sIL-2Rα in 38 recipients of a renal transplant (32 treated with daclizumab and six controls). sIL-2Rα was measured every 2weeks after transplantation in serum and urine with Immulite® IL-2R, a solid-phase enzyme-linked immunosorbent assay (ELISA).ResultsIn the control population, the fractional excretion of sIL-2Rα was relatively constant with a median value of 1.7%± 0.5%. In daclizumab-treated patients, sIL-2Rα was not detectable in the urine immediately after the administration of daclizumab. sIL-2Rα became detectable in the urine at a mean of 8 ± 3weeks after transplantation. In additional experiments, serum compounds were separated by size-exclusion chromatography and sIL-2Rα was measured in the collected fractions. In the control patients, sIL-2Rα was only present in the low-molecular-weight fractions of serum. In contrast, in daclizumab-treated patients evaluated several weeks after transplantation, sIL-2Rα was merely detected in the high-molecular-weight fractions of serum. During follow-up there was a relative shift of sIL-2Rα from the high- to the low-molecular-weight fractions and this coincided with normalization of sIL-2Rα excretion.ConclusionDaclizumab inhibits the renal excretion of sIL-2Rα by the formation of a complex with sIL-2Rα in serum, which is too large for glomerular filtration. Measurement of urinary sIL-2Rα may provide information on the concentration of anti-IL-2Rα mAb in serum