Watanabe Mizuho, Kaneko Hideo, Shikano Hiroaki, Aoki Minako, Sakaguchi Heima, Matsui Eiko, Inoue Ryosuke, Kato Zenichiro, Kasahara Kimiko, Fukutomi Osamu, Kondo Tomio, Kondo Naomi
Department of Pediatrics, Gifu University School of Medicine, Japan.
J Allergy Clin Immunol. 2002 Apr;109(4):669-75. doi: 10.1067/mai.2002.122158.
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.
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.
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.
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.
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.
