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

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Abstract
Summary. 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.