Immunogenicity of a mammalian cell-derived recombinant human growth hormone preparation during long-term treatment.
The development of anti-human growth hormone (anti-hGH) and anti-host-cell protein antibodies to recombinant hGH (rhGH) of mammalian cell origin was determined in 395 children (304 GH deficiency; 91 Turner syndrome) undergoing long-term treatment (up to 54 months) for growth disorders. In all patients, blood samples were obtained prior to and every 2-3 months during treatment, and analyzed at a central laboratory for anti-hGH antibodies by RIA and antibodies to host-cell antigens by ELISA. During the first 24 months of treatment, 9 (3%) of the 304 patients with GH deficiency developed antibodies to rhGH for longer than 3 months. However, persistent antibodies were seen in only 2 patients, both of whom had proven hGH-N gene defects. In the remaining 7 (2%) anti-rhGH-antibody-positive patients, antibody concentrations showed a tendency to increase for 3-12 months, irrespective of the time of onset of measurable concentrations, and declined thereafter. In these patients, binding capacities were between 0.01 and 0.1 mg/l, and binding affinities were between 7 x 10(8) and 8 x 10(9) l/mol. Height velocity was unaffected in these children. None of the 91 patients with Turner syndrome developed persistent anti-hGH antibodies. Further, no child developed antibodies to host-cell antigens during treatment with rhGH of mammalian cell origin.
Zeisel
H J
HJ
University Children's Hospital, Freiburg, FRG.
Lutz
A
A
von Petrykowski
W
W
D000293:Adolescent; D000818:Animals; D000906:Antibodies / Q000032:analysis; D000917:Antibody Formation; D002460:Cell Line / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D013006:Growth Hormone / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D011863:Radioimmunoassay; D011994:Recombinant Proteins; D013997:Time Factors; D014424:Turner Syndrome / Q000188:drug therapy*
D000906:Antibodies; D011994:Recombinant Proteins; D013006:Growth Hormone