Different Gm allotype amounts in human intravenous immunoglobulin (IVIG) preparations; survival of foreign Gm allotypes in immunodeficient patients

摘要

IVIG is used as standard replacement therapy in primary antibody deficiency. IVIG consists mainly of IgG. IVIG preparations were investigated with respect to Gm allotypes, which are characterized by various amino acid epitopes in the constant heavy chains of the IgG subclasses IgG1, IgG2 and IgG3. The alternative allelic Gm allotypes G1m(a) and G1m(f) of IgG1, G2m(n) and G2m(”) of IgG2 and G3m(g) and G3m(b) of IgG3 were measured by sensitive competitive ELISAs for G1m(a), G1m(f), G2m(n) and G3m(b). IgG subclass levels were quantified by radioimmunodiffusion (RID). Gm allotype quantities differed significantly in various IVIG products, with different products having half or double the amount of the different Gm allotypes. The results show the effect of the different manufacturing processes, but also indicate different physicochemical properties of Gm allotypes within the same IgG subclass. The different contents of Gm allotypes might be one reason for the variable levels of specific antibodies found in IVIG products. Immunodeficient patients with homozygous expression of Gm allotypes from IGHCG1, IGHCG2 and IGHCG3 were tested after infusion of foreign Gm allotypes. A prolonged survival was found for the G2m allotype, G2m(n), compared with G1m allotypes. Different half-lives were found for the alternative G1m(a) and G1m(f) allotypes, within the same IgG1 subclass.