Gm Allotype Genes and Gene Dosage Affecting Both IgG Subclass and IgE Levels in Atopic Patients

Of 32 unrelated children with serum IgE > 1,000 U/ml, 17 were found to have infection proneness according to standard clinical criteria, and 15 were not infection prone. There were no statistical differences between these 2 groups of children with regard to age, sex, serum IgE levels or prevalence of asthma. However, the prevalence of eczema was significantly lower in the infection-prone group (p = 0.035). Of greater interest was the finding that 7 children in the infection-prone group had IgG subclass and/or IgA deficiency compared with none in the non-infection-prone group (p = 0.006). These results suggest that IgG subclass studies may be warranted in children with markedly elevated levels of serum IgE and proneness to infection.

Section: Discussionsupporting

confidence: 81%

Immunoglobulin G Subclass Deficiency in Children with High Levels of Immunoglobulin E and Infection Proneness

Loh

Thong

Ferrante

1990

“…In addition, an association between this Gm(f,f; n,n;b,b) genotype o f atopic children and significantly in creased serum IgG4 and IgE levels has been observed [3]. Increased IgG4 has earlier been noted in patients with the most severe atopic disease [4], We therefore suggested the homozygous Gm(f,f;n,n;b,b) phenotype as a marker for se vere atopy [3], Complex genetic and environmental factors have been identified which contribute to the manifestation of atopy. There is evidence that inheritance of the immune response in atopy is polygenic.…”

Section: Introductionmentioning

confidence: 89%

“…Glm(f) and G2m(n) determinations were done by radial immuno diffusion [14] with murine monoclonal antisera specific to these allo types: anti-Glm(f) 6006-10 clone SG-16 and anti-G2m(n) 6016 10 clone SH-21 (Sigma, St Louis, Mo., USA) published previously [2,3], Forthc determination of homozygosity and heterozygosity ofG2m(n), a double diffusion assay [15] was used with the monoclonal reagents: anti-G2m(n) 6016 10 clone SH 21 and anti-lgG2 HP 6014 (Sigma). The frequency figures o f Gm markers were compared with a normal Swedish population consisting of 157 healthy blood donors 96 males and 61 females [16].…”

Section: Methodsmentioning

confidence: 99%

“…Atopic children predominantly expressed Glm(f) for the IGHCGl gene, G2m(n) for the IGHCG2 and G3m(b) for IGHCG3, namely the homozygous Gm(f,f;n,n;b,b) geno type [2]. In addition, an association between this Gm(f,f; n,n;b,b) genotype o f atopic children and significantly in creased serum IgG4 and IgE levels has been observed [3]. Increased IgG4 has earlier been noted in patients with the most severe atopic disease [4], We therefore suggested the homozygous Gm(f,f;n,n;b,b) phenotype as a marker for se vere atopy [3], Complex genetic and environmental factors have been identified which contribute to the manifestation of atopy.…”

Section: Introductionmentioning

confidence: 96%

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Development of Allergy to Laboratory Animals Is Associated with Particular Gm and HLA Genes

Oxelius

Sjöstedt²,

Willers

et al. 1996

Self Cite

To find out whether IgG genes are involved in atopy we studied 26 of 101 laboratory technicians who had developed laboratory animal allergy (LAA). The genes for the constant region of the heavy chains of IgG subclasses were analyzed by serum Gm allotypes, representing products on allelic level of the IGHCG1, IGHCG2 and IGHCG3 on chromosome 14q32. There was a significantly increased frequency of the Gm(f,f;n,n;b,b) genotype (57.7 instead of 22.3%, p < 0.001) representing IgG1, IgG2 and IgG3 molecules and in particular increased frequency of Gm genotypes with the homozygous expression of G2m (nn) (69.2 instead of 27.4%, p < 0.001) and of the Gm(fnb) haplotype (75 instead of 44.8%, p < 0.001) compared to a normal Caucasian population. An increased HLA-DR4 content of the LAA group (61.5 instead of 33.7%, p < 0.01) was further investigated for Gm allotypes. Among 16 HLA-DR4 LAA individuals, the Gm(f,f;n,n;b,b) genotype (56.3 instead of 22.3%, p < 0.01) and the Gm genotypes with the homozygous expression G2m(n, n) (62.6 instead of 27.4%, p < 0.01) dominated. However, the HLA-DR4 frequency among Gm(f,f;n,n;b,b) of LAA patients did not deviate from the frequency of healthy individuals of the same Gm genotype. The increased frequency of HLA-DR4 antigen in LAA patients might be due to its association to the Gm(f,f;n,n;b,b) genotype. This study supports the following concept: the susceptibility of developing LAA is associated with Gm allotypes Glm(f) expressed from IGHCG1, G2m(n) from IGHCG2 and G3m(b) from IGHCG3 on both alleles situated close to IGHCE on chromosome 14q32. The association of LAA to Gm allotypes [Gm(f,f;n,n;b,b)] expressed from chromosome 14q32 and of HLA class II antigens (HLA-DR4) expressed from chromosome 6p21.3 further confirms the polygenic inheritance of the immune response in atopy.

“…The IGHG association is found in patients with clinical allergy and increased IgE levels, increased IgG4 levels, a family history of allergy, and in technicians exposed to laboratory animals developing laboratory animal allergy [5,6,21,22,23]. The alternative IGHG haplotypes have been found with different pathways of immune regulation in patients with asthma [23].…”

Section: Introductionmentioning

confidence: 99%

From Genotypes of Immunoglobulin Constant Heavy G Chains (Fcγ) (GM) Genes <b><i>(IGHG)</i></b> to Phenotypes in Childhood Asthma

Oxelius

2012

Self Cite

Background: IgE-mediated allergy is associated with immunoglobulin heavy constant G chain (Fcγ) (GM) genes (IGHG) on chromosome 14q32.3. Investigation of the alternative GM allotypes of γ3, γ1 and γ2 chains has disclosed new structural and functional IgG subclasses and B-cell variants, with possible effects on childhood asthma. Objective: To investigate different IGHG (GM) gene complexes in a childhood asthma population for allergy parameters. Methods:IGHG alleles and correlated allotypic (allelic) IgG subclass levels were analyzed with a sensitive indirect competitive ELISA in 10-year-old children with bronchial asthma. Individual IGHG diplotype-, genotype- and haplotype-related B cells were compared for allelic IgG subclass levels, IgE sensitization, IgE, IgA and IgM levels, and numbers of peripheral blood eosinophils and lymphocytes. Results: The group with homozygous IGHG*bfn/*bfn (B1/B1 cells) demonstrated low IgG1*f levels (p < 0.001) but increased IgG2*n levels (p < 0.001) together with increasd IgE and IGHG2*n gene dose-dependent IgE sensitization (atopic phenotype). The IGHG*bf–n/*bf–n (B2/B2 cells) demonstrated low IgG1*f (p < 0.05) and IgG2*–n (p < 0.001) and the IGHG*ga–n/*ga–n (B4/B4 cells) low IgG1*a (p < 0.001) and IgG2*–n (p < 0.02) together with low IgE sensitization (non-atopic phenotype). B*^bfn (B1) and B*^bf–n (B2) demonstrated increased numbers of peripheral blood eosinophils, compared to B*^gan (B4) cells, which demonstrated increased peripheral blood CD8 lymphocytes instead. Conclusion:IGHG diplotypes present different phenotypes in childhood asthma. The IGHG2*n dose relationship to IgE sensitization and increased IgG2*n levels in IgE sensitized are risk markers for IgE-mediated asthma. The opposite IGHG2*–n presents non-IgE-mediated asthma and IgG subclass deficiencies.