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From Genotypes of Immunoglobulin Constant Heavy G Chains (Fcγ) (GM) Genes (IGHG) to Phenotypes in Childhood Asthma.

Oxelius, Vivi-Anne LU (2012) In International Archives of Allergy and Immunology 159(1). p.94-102
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Fc gamma, Allelic IgG subclasses, GM allotypes, IgE, Immunodeficiency, Phenotypes, IGHG diagnostic tests, Immunoglobulin constant heavy G chain
in
International Archives of Allergy and Immunology
volume
159
issue
1
pages
94 - 102
publisher
Karger
external identifiers
  • wos:000305801000012
  • pmid:22573066
  • scopus:84860871538
ISSN
1423-0097
DOI
10.1159/000335592
language
English
LU publication?
yes
id
934a4b86-e958-4f39-b673-16789fa07588 (old id 2608967)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22573066?dopt=Abstract
date added to LUP
2012-06-03 13:12:25
date last changed
2017-01-01 04:07:44
@article{934a4b86-e958-4f39-b673-16789fa07588,
  abstract     = {Background: <br/><br>
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. <br/><br>
<br/><br>
Objective: <br/><br>
To investigate different IGHG (GM) gene complexes in a childhood asthma population for allergy parameters. <br/><br>
<br/><br>
Methods: <br/><br>
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. <br/><br>
<br/><br>
Results: <br/><br>
The group with homozygous IGHG*bfn/*bfn (B1/B1 cells) demonstrated low IgG1*f levels (p &lt; 0.001) but increased IgG2*n levels (p &lt; 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 &lt; 0.05) and IgG2*-n (p &lt; 0.001) and the IGHG*ga-n/*ga-n (B4/B4 cells) low IgG1*a (p &lt; 0.001) and IgG2*-n (p &lt; 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. <br/><br>
<br/><br>
Conclusion: <br/><br>
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.},
  author       = {Oxelius, Vivi-Anne},
  issn         = {1423-0097},
  keyword      = {Fc gamma,Allelic IgG subclasses,GM allotypes,IgE,Immunodeficiency,Phenotypes,IGHG diagnostic tests,Immunoglobulin constant heavy G chain},
  language     = {eng},
  number       = {1},
  pages        = {94--102},
  publisher    = {Karger},
  series       = {International Archives of Allergy and Immunology},
  title        = {From Genotypes of Immunoglobulin Constant Heavy G Chains (Fcγ) (GM) Genes (IGHG) to Phenotypes in Childhood Asthma.},
  url          = {http://dx.doi.org/10.1159/000335592},
  volume       = {159},
  year         = {2012},
}