Minegishi Yoshiyuki, Karasuyama Hajime
Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Curr Allergy Asthma Rep. 2008 Sep;8(5):386-91. doi: 10.1007/s11882-008-0075-x.
Hyper-IgE syndrome (HIES) is a complex primary immunodeficiency characterized by high serum IgE, chronic eczematoid dermatitis, and recurrent extracellular bacterial infections. Two types of HIES have been reported: type 1 and type 2. Type 1 HIES displays abnormalities in multiple systems, including the skeletal, dental, and immune systems, whereas type 2 shows abnormalities confined to the immune system. We recently identified hypomorphic mutations in the signal transducer and activator of transcription 3 (STAT3) gene in type 1 HIES and a null mutation in the tyrosine kinase 2 (Tyk2) gene, accompanied by susceptibility to intracellular bacteria in type 2 HIES. Analyses of cytokine responses in both types of HIES revealed that severe defects in the signal transduction for multiple cytokines, including interleukin-6 and interleukin-23, are leading to impaired T-helper type 17 function. These findings suggest that HIES is caused by the defects in multiple cytokine signals and that the susceptibility to various infections in HIES is associated with the T-helper type 17 defect.
高免疫球蛋白E综合征（HIES）是一种复杂的原发性免疫缺陷病，其特征为血清IgE水平升高、慢性湿疹样皮炎和反复的细胞外细菌感染。已报道了两种类型的HIES：1型和2型。1型HIES在多个系统中表现出异常，包括骨骼、牙齿和免疫系统，而2型仅在免疫系统中表现出异常。我们最近在1型HIES中发现了信号转导和转录激活因子3（STAT3）基因的低功能突变，以及在2型HIES中发现了酪氨酸激酶2（Tyk2）基因的无效突变，并伴有对细胞内细菌的易感性。对两种类型HIES的细胞因子反应分析表明，包括白细胞介素-6和白细胞介素-23在内的多种细胞因子的信号转导严重缺陷，导致辅助性T细胞17功能受损。这些发现表明，HIES是由多种细胞因子信号缺陷引起的，并且HIES对各种感染的易感性与辅助性T细胞17缺陷有关。
