Ambrosino D

Atherton A

Aurivillius M

Finkelman FD

Gustafsson PM

Jönsson G

Legrand L

Namboodiri AM

Nimmerjahn F

Oxelius VA

Palmer LJ

Pandey JP

Sleiman PMA

Vivi-Anne Oxelius

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; IgE-mediated allergy is associated with immunoglobulin heavy constant G chain (Fcγ) (GM) genes &lt;i&gt;(IGHG)&lt;/i&gt; 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. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To investigate different &lt;i&gt;IGHG&lt;/i&gt; (GM) gene complexes in a childhood asthma population for allergy parameters. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt;&lt;i&gt;IGHG&lt;/i&gt; 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 &lt;i&gt;IGHG&lt;/i&gt; 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. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The group with homozygous &lt;i&gt;IGHG&lt;/i&gt;*&lt;i&gt;bfn/&lt;/i&gt;*&lt;i&gt;bfn&lt;/i&gt; (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 &lt;i&gt;IGHG2&lt;/i&gt;*&lt;i&gt;n &lt;/i&gt;gene dose-dependent IgE sensitization (atopic phenotype). The &lt;i&gt;IGHG&lt;/i&gt;*&lt;i&gt;bf–n&lt;/i&gt;/*&lt;i&gt;bf–n&lt;/i&gt; (B2/B2 cells) demonstrated low IgG1*f (p &lt; 0.05) and IgG2*–n (p &lt; 0.001) and the &lt;i&gt;IGHG&lt;/i&gt;*&lt;i&gt;ga–n/&lt;/i&gt;*&lt;i&gt;ga–n&lt;/i&gt; (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*&lt;sup&gt;bfn&lt;/sup&gt; (B1) and B*&lt;sup&gt;bf–n&lt;/sup&gt; (B2) demonstrated increased numbers of peripheral blood eosinophils, compared to B*&lt;sup&gt;gan&lt;/sup&gt; (B4) cells, which demonstrated increased peripheral blood CD8 lymphocytes instead. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt;&lt;i&gt;IGHG&lt;/i&gt; diplotypes present different phenotypes in childhood asthma. The &lt;i&gt;IGHG2&lt;/i&gt;*n dose relationship to IgE sensitization and increased IgG2*n levels in IgE sensitized are risk markers for IgE-mediated asthma. The opposite &lt;i&gt;IGHG2&lt;/i&gt;*&lt;i&gt;–n&lt;/i&gt; presents non-IgE-mediated asthma and IgG subclass deficiencies.</jats:p

Crossref

International Archives of Allergy and Immunology

From Genotypes of Immunoglobulin Constant Heavy G Chains (Fcγ) (GM) Genes &lt;b&gt;&lt;i&gt;(IGHG)&lt;/i&gt;&lt;/b&gt; to Phenotypes in Childhood Asthma

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

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

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