The Role of Aggregated hGH in the Therapy of hGH-Deficient Children*

Abstract

Clinical grade hGH prepared from acetone-preserved pituitaries contains significant quantities of aggregated hGH. The growth promoting and immunogenic potential of the aggregatedhGH was evaluated by comparing the growth and antibody response in patients receiving either clinical grade hGH or monomeric hGH prepared from clinical grade hGH. The group receiving clinical grade hGH (2 U, three times per week) had average growth rates of 1.4 and 7.0 cmDyear before and during the 1st year of therapy, respectively. The group receiving monomeric hGH (the amount contained in 2 IU of clinical grade hGH, three times per week) had average growth rates of 1.0 and8.9 cm/year before and during therapy, respectively. Five of nine patients receiving clinical grade hGH developed antibodies to monomeric hGH within the 1st year of therapy and two of three patients receiving monomeric hGH also developed antibodies to hGH within 6 months from onset of therapy. The monomeric hGH preparation was observed to contain small amounts of aggregated hGH by the end of a 3-month therapy period. The peripheral mononuclear leukocytes from the patients bound aggregated hGH in about 89% of the determinations. The average amounts of polymeric, dimeric, and monomeric hGH bound by the leukocytes was 20.4, 9.5, and 0.28 ng⁄10⁹ cells, respectively. Monomeric hGH binding was only observed in association with circulating antibodies to hGH. It is concluded that: 1) most if not all of the biological activity of clinical grade hGH (prepared from acetonepreserved glands) is contained in the monomeric hGH fraction; 2) aggregated hGH may be the immunogenic agent in clinical grade hGH, but the monomeric hGH may also be immunogenic; and 3) the immunogenic potential or aggregated hGH may result from its ability to bind to immunocompetent cells.