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儿童期血清Gm同种异型的发育

Serum Gm allotype development during childhood.

作者信息

Oxelius V A, Aurivillius M, Carlsson A M, Musil K

机构信息

Department of Pediatrics and Clinical Immunology, University Hospital, Se-221 85 Lund, Sweden.

出版信息

Scand J Immunol. 1999 Oct;50(4):440-6. doi: 10.1046/j.1365-3083.1999.00618.x.

DOI:10.1046/j.1365-3083.1999.00618.x
PMID:10520186
Abstract

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.

摘要

Gm同种异型是IgG分子免疫球蛋白重链G(IGHG)的基因变体,由14号染色体q32编码,其特征在于恒定重链G的氨基酸表位存在差异,并以孟德尔方式遗传。Gm同种异型对IgG亚类水平有影响,并且已经给出了成人不同Gm基因型的血清Gm同种异型水平。对430名1至15岁的健康儿童进行了血清Gm同种异型和IgG亚类检测,这些儿童来自六种最常见的Gm基因型,不同年龄组采用竞争性酶联免疫吸附测定法和放射免疫扩散法进行检测。给出了IgG1的G1m(a)和G1m(f)、IgG2的G2m(n)和G2m(-n)以及IgG3的G3m(g)和G3m(b)的含量(以g/l为单位)。结果显示了IgG1、IgG2和IgG3内替代Gm同种异型的不同成熟速率。与来自γ2基因座的G2m(-n)相比,G2m(n)的发育明显延迟。这一现象在比较纯合G2m(-n-n)和G2m(nn)个体的IgG2水平时被发现,但在杂合G2m(n-n)基因型中也可见。在杂合G1m(af)个体中,来自γ1基因座的G1m(f)水平在很大程度上但不恒定地显著高于G1m(a)水平。在纯合G1m基因型中,相同年龄的G1m(aa)与G1m(ff)相比,其中一种占主导地位,有时差异显著。3岁以上纯合G3m(bb)个体γ3基因座的G3m(b)血清水平与纯合G3m(gg)个体的G3m(g)水平相比显著升高。然而,在杂合G3m(gb)个体中,G3m(b)的优势并不明显。在Gm(f;n;b)单倍型中,G1m(f)分子发育相对较快,G2m(n)发育延迟。相比之下,在Gm(a;-n;g)单倍型中,G1m(a)发育延迟,G2m(-n)增强。血清G2m(n)发育延迟与儿童期血清IgA发育相当。同一IgG亚类内Gm同种异型的不同成熟速率为儿童期抗体反应的变化提供了进一步解释。Gm同种异型的定量测定提供了IGHG基因活性的信息。这种基因变异构成了评估儿童期不同疾病中IgG抗体的额外依据。

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