title: Cytokine imbalance in hyper-IgE syndrome: reduced expression of transforming growth factor beta and interferon gamma genes in circulating activated T cells.
abstract: Hyper-IgE syndrome (HIES) is a primary immunodeficiency disease characterized by recurrent infections and marked immunoglobulin (Ig)E elevation. To assess the proper T-cell defects of HIES, the cytokine profile of naturally activated T cells was compared between HIES, atopic dermatitis and chronic granulomatous disease (CGD). Intracellular flow cytometric analysis after in vitro stimulation showed no difference in the proportion of interferon (IFN)gamma- or interleukin 4 (IL-4)-producing T cells among these diseases. Quantitative polymerase chain reaction (PCR) for the cytokine genes was performed using circulating highly fractionated HLA-DR+ and HLA-DR- T cells. The IFNgamma/IL-4 or IFNgamma/IL-10 ratios were lower in HLA-DR+ T cells of HIES than in CGD (P = 0.0106, 0.0445), but did not differ between HIES and atopy. The transforming growth factor-beta (TGFbeta)/IL-4 ratio in HLA-DR+ T cells of HIES was lower than that of atopy (0.0106) or CGD (0.0062). The TGFbeta/IL-4 ratio in HLA-DR- T cells of HIES was also lower than that of atopy (0.0285). Stepwise logistic regression analysis identified TGFbeta/IL-4 ratios in HLA-DR+ (0.0001) or HLA-DR- (0.0086) T cells as the most powerful parameters to distinguish HIES from atopy and/or CGD. Serum IgE levels negatively correlated with IFNgamma/IL-4 (0.0108), IFNgamma/IL-10 (0.0254), or TGFbeta/IL-4 (0.0163) ratios in HLA-DR+, but not HLA-DR-, T cells. These results suggested that the in vivo activated T cells of HIES did not sufficiently express the IFNgamma and TGFbeta genes, which could affect IL-4-dependent IgE production. The reduced TGFbeta expression may involve the indigenous T-cell defects of HIES.
authors.affiliation: Department of Paediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ohgas@pediatr.med.kyushu-u.ac.jp
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nomura
authors.forename: Kenji
authors.initials: K
authors.lastname: Ihara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takahata
authors.forename: Naohiro
authors.initials: N
authors.lastname: Suga
authors.forename: Hideki
authors.initials: H
authors.lastname: Akeda
authors.forename: Rumiko
authors.initials: R
authors.lastname: Shibata
authors.forename: Jun
authors.initials: J
authors.lastname: Okamura
authors.forename: Naoko
authors.initials: N
authors.lastname: Kinukawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003876:Dermatitis, Atopic / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006105:Granulomatous Disease, Chronic / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D007589:Job Syndrome / Q000175:diagnosis / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma