Role of Aggregated Human Growth Hormone (hGH) in Development of Antibodies to hGH*

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Abstract
By measuring [125I]hGH [human growth hormone] binding in the plasma of hGH-deficient children at 3-4 mo. intervals during hGH therapy with hGH prepared by Raben''s method, 3 patterns of antibody formation were defined. One group of patients developed antibodies by 3 mo. of therapy that persisted despite the length or type of hGH therapy. Their antibodies were characterized by a low affinity (1.49 .times. 109 M-1) and a high capacity (29 nmol/l plasma). The development or presence of antibodies adversely affected the growth rate in only 1 patient in this group. This patient''s antibodies were characterized by the highest capacity (1235 nmol/l plasma) and lowest affinity (0.044 .times. 109 M-1). The capacity decreased to 134 nmol/l plasma upon switching to a hGH preparation without aggregated hGH. The 2nd group developed antibodies to hGH by 6-9 mo. of therapy, but [125I]hGH binding by the plasma returned to control levels by 20 mo. of therapy. The antibodies of this group were characterized by a higher affinity (12.7 .times. 109 M-1) and a lower capacity (0.9 nmol/l plasma) than the group with antibodies. This group had received hGH with less than 5% aggregated hGH. The 3rd group did not develop significant [125I]hGH binding in the plasma despite prolonged therapy with multiple hGH preparations. Several patients were treated solely with recent hGH preparations from the National Pituitary Agency which contain less than 10% aggregated hGH compared to earlier preparations containing more than 20%. The incidence (44%) of significant [125I]hGH binding by these patients'' plasmas was similar to that of patients receiving hGH with aggregated hGH; hGH binding by the plasma of most of these patients was characteristic of that of patients with transient antibodies. Apparently the development of antibodies to hGH during therapy is dependent on individual susceptibility and the presence of aggregated hGH in the hGH preparation; the antibody response is more likely to be transient if the content of aggregated hGH is low and the eventual incidence of significant hGH binding in plasma of patients who receive hGH prepared by Raben''s method without aggregated hGH will be the same as that observed in patients receiving hGH prepared by other methods.