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


CONCLUSIONS
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.
ter Meulen
Cornelis G
CG
Department of Internal Medicine, Division of Nephrology, University Medical Center Nijmegen, Nijmegen, The Netherlands. C.termuelen@nier.umcn.nl
Göertz
Joop H C
JH
Klasen
Ina S
IS
Verweij
Carla M T A
CM
Hilbrands
Luuk B
LB
Wetzels
Jack F M
JF
Hoitsma
Andries J
AJ
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood; D007201:Indicator Dilution Techniques; D053645:Interleukin-2 Receptor alpha Subunit; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D011446:Prospective Studies; D018123:Receptors, Interleukin / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D012995:Solubility; D014556:Urine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C508017:IL2RA protein, human; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin; D000077561:Daclizumab