Serum Gm allotype development during childhood

Gm allotypes are genetic variants of the immunoglobulin heavy G chains (IGHG) of IgG molecules, coded from chromosome 14q32, characterized by differences in amino acid epitopes of the constant heavy G chains and inherited in the Mendelian manner. Gm allotypes have influence on IgG subclass levels, and serum Gm allotype levels have been given for different Gm genotypes in adults. Four hundred and thirty healthy children, aged 1-15 years, were examined for serum Gm allotypes and IgG subclasses from the six most common Gm genotypes and different age groups were measured using competitive enzyme-linked immunosorbant assay and radial immunodiffusion methods. Quantities (in g/l) of G1m(a) and G1m(f) of IgG1, G2m(n) and G2m(-n) of IgG2 and G3m(g), and G3m(b) of IgG3 are given. Different maturation rates of the alternative Gm allotypes within IgG1, IgG2 and IgG3 were shown. G2m(n) development was strikingly retarded compared with G2m(-n) from the gamma2 locus. This was found comparing IgG2 levels from homozygous G2m(-n-n) and G2m(nn) individuals, but was also seen in heterozygous G2m(n-n) genotypes. From the gamma1 locus G1m(f) levels dominated significantly, but inconstantly, over G1m(a) levels in heterozygous G1m(af) individuals. In homozygous G1m genotypes, G1m(aa) compared with G1m(ff) of the same age, one or the other dominated, sometimes significantly. Serum levels of G3m(b) from the gamma3 locus of homozygous G3m(bb) individuals were increased significantly compared with G3m(g) levels of homozygous G3m(gg) individuals, in ages over 3 years. However, in heterozygous G3m(gb) individuals G3m(b) dominance was not evident. There is a relatively rapid development of G1m(f) molecules and a retarded development of G2m(n) in the Gm(f;n;b) haplotype. In comparison, G1m(a) is retarded and G2m(-n) is enhanced in the Gm(a;-n;g) haplotype. The retarded serum G2m(n) development is comparable with serum IgA development during childhood. Different maturation rates of Gm allotypes within the same IgG subclass provide further explanation for the variation of the antibody response during childhood. Quantitative Gm allotype determinations give information of the activity from IGHG genes. The genetic variation constitutes an additional basis for evaluation of IgG antibodies in different diseases in childhood.