Cytokine imbalance in hyper-IgE syndrome: Reduced expression of transforming growth factor β and interferon γ genes in circulating activated T cells

Shouichi Ohga, Akihiko Nomura, Kenji Ihara, Yasushi Takahata, Naohiro Suga, Hideki Akeda, Rumiko Shibata, Jun Okamura, Naoko Kinukawa, Toshiro Hara

研究成果: Contribution to journalArticle査読

25 被引用数 (Scopus)

抄録

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)γ- 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 IFNγ/IL-4 or IFNγ/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-β (TGFβ)/IL-4 ratio in HLA-DR+ T cells of HIES was lower than that of atopy (0.0106) or CGD (0.0062). The TGFβ/IL-4 ratio in HLA-DR- T cells of HIES was also lower than that of atopy (0.0285). Stepwise logistic regression analysis identified TGFβ/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 IFNγ/IL-4 (0.0108), IFNγ/IL-10 (0.0254), or TGFβ/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 IFNγ and TGFβ genes, which could affect IL-4-dependent IgE production. The reduced TGFβ expression may involve the indigenous T-cell defects of HIES.

本文言語英語
ページ(範囲)324-331
ページ数8
ジャーナルBritish Journal of Haematology
121
2
DOI
出版ステータス出版済み - 4 2003

All Science Journal Classification (ASJC) codes

  • 血液学

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