title: Predominant expression of 950delCAG of IL-18R alpha chain cDNA is associated with reduced IFN-gamma production and high serum IgE levels in atopic Japanese children.
abstract: BACKGROUND
  We previously reported that serum IgE levels were negatively correlated with the amount of IFN-gamma produced by phytohemagglutinin-stimulated or IL-12-stimulated PBMCs and that one of the mechanisms of the pathogenesis of atopy was the reduced IFN-gamma production, which led to upregulated IgE production.
  
  
  OBJECTIVE
  IL-18 is also known to be a strong inducer of IFN-gamma production. However, it has not yet been determined whether IL-18 is associated with atopic disease.
  
  
  METHODS
  We investigated the response to IL-18 or IL-12 stimulation and the sequence of IL-18 receptor (IL-18R) alpha chain cDNA in 41 nonatopic controls and 39 atopic patients.
  
  
  RESULTS
  Serum IgE level was negatively correlated with IFN-gamma production by PBMCs stimulated with IL-18. The IL-18R alpha chain cDNA of atopic patients was sequenced. We identified a 3-base deletion of the IL-18R alpha chain cDNA (950delCAG ), which was generated by alternative splicing, as determined on the basis of genomic sequence data for the IL-18R alpha chain gene. PBMCs with the predominant expression of 950delCAG significantly showed the reduced IFN-gamma production after IL-18 stimulation. There was a significant difference in the expression pattern of the IL-18R alpha chain transcript between the atopic patients and the nonatopic controls.
  
  
  CONCLUSIONS
  According to these results, the dominant expression of the 950delCAG transcript of IL-18R alpha chain cDNA, which was associated with reduced IFN-gamma production by IL-18 stimulation and high serum IgE levels, is predisposition to some atopic diseases.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Kaneko
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shikano
authors.forename: Minako
authors.initials: M
authors.lastname: Aoki
authors.forename: Heima
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Eiko
authors.initials: E
authors.lastname: Matsui
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Inoue
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Kato
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kasahara
authors.forename: Osamu
authors.initials: O
authors.lastname: Fukutomi
authors.forename: Tomio
authors.initials: T
authors.lastname: Kondo
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018076:DNA, Complementary / Q000032:analysis*; D017353:Gene Deletion; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood*; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000494:pharmacology; D053727:Interleukin-18 Receptor alpha Subunit; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000235:genetics*; D053724:Receptors, Interleukin-18
chemical_list: D018076:DNA, Complementary; C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D007073:Immunoglobulin E; D007371:Interferon-gamma