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.