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.
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.
Watanabe
Mizuho
M
Department of Pediatrics, Gifu University School of Medicine, Japan.
Kaneko
Hideo
H
Shikano
Hiroaki
H
Aoki
Minako
M
Sakaguchi
Heima
H
Matsui
Eiko
E
Inoue
Ryosuke
R
Kato
Zenichiro
Z
Kasahara
Kimiko
K
Fukutomi
Osamu
O
Kondo
Tomio
T
Kondo
Naomi
N
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
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