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

Abstract

Background: Daclizumab (+/-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 alpha (sIL-2R alpha; +/-45 kD), and thus may influence the glomerular filtration of sIL-2R alpha.

Methods: We have studied the influence of daclizumab on the renal excretion of sIL-2R alpha in 38 recipients of a renal transplant (32 treated with daclizumab and six controls). sIL-2R alpha was measured every 2 weeks after transplantation in serum and urine with Immulite IL-2R, a solid-phase enzyme-linked immunosorbent assay (ELISA).

Results: In the control population, the fractional excretion of sIL-2R alpha was relatively constant with a median value of 1.7%+/- 0.5%. In daclizumab-treated patients, sIL-2R alpha was not detectable in the urine immediately after the administration of daclizumab. sIL-2R alpha became detectable in the urine at a mean of 8 +/- 3 weeks after transplantation. In additional experiments, serum compounds were separated by size-exclusion chromatography and sIL-2R alpha was measured in the collected fractions. In the control patients, sIL-2R alpha was only present in the low-molecular-weight fractions of serum. In contrast, in daclizumab-treated patients evaluated several weeks after transplantation, sIL-2R alpha was merely detected in the high-molecular-weight fractions of serum. During follow-up there was a relative shift of sIL-2R alpha from the high- to the low-molecular-weight fractions and this coincided with normalization of sIL-2R alpha excretion.

Conclusion: Daclizumab inhibits the renal excretion of sIL-2R alpha by the formation of a complex with sIL-2R alpha in serum, which is too large for glomerular filtration. Measurement of urinary sIL-2R alpha may provide information on the concentration of anti-IL-2R alpha mAb in serum.