Clinical Manifestations, Etiology, and Pathogenesis of the Hyper-IgE Syndromes
Clinical Manifestations, Etiology, and Pathogenesis of the Hyper-IgE Syndromes
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DOI：
10.1203/pdr.0b013e31819dc8c5
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发表时间：
2009-05-01
影响因子：
3.6
通讯作者：
Holland, Steven M.
中科院分区：
文献类型：
--
作者：
Freeman, Alexandra F.;Holland, Steven M.
常染色体显性高免疫球蛋白E综合征(ADH-IES)是一种罕见的原发免疫缺陷，以湿疹、反复发作、皮肤和肺部感染、血清IgE升高以及各种结缔组织、骨骼和血管异常为特征。最近发现信号转导和转录激活因子3(STAT3)突变是大多数病例的原因，然而，不同特征的发病机制仍不清楚。一种独特的综合征，称为常染色体隐性遗传性HIEs(AR-HIEs)，表现为严重的湿疹，反复发生的细菌和病毒皮肤感染，以及鼻窦肺部感染。与STAT3缺陷的HIEs不同，AR-HIEs缺乏结缔组织和骨骼表现，但神经异常增加。在这篇综述中，我们讨论了这两个综合征的临床表现、遗传病因和免疫异常。此外，我们还讨论了STAT3缺乏的动物模型，为HIEs的发病机制提供了深入的认识。进一步了解STAT3如何导致HIE的不同表现，将使我们能够开发出针对HIE以及许多表现的更具体的治疗方法，如脊柱侧弯、反复发生的葡萄球菌感染和湿疹，这些在普通人群中很常见。(儿科研究报告65：32R-37R，2009)
Autosomal dominant Hyper-IgE syndrome (ADH-IES) is a rare primary immunodeficiency characterized by eczema, recurrent,skin and lung infections, elevated serum IgE, and various connective tissue, skeletal, and vascular abnormalities. Mutations in signal transducer and activator of transcription 3 (STAT3) have recently been found to account for most cases however, the pathogenesis of the varied features remains poorly defined. A distinct syndrome, known as autosomal recessive HIES (AR-HIES) manifests as severe eczema, recurrent bacterial and viral skin infections, and sinopulmonary infections. As opposed to STAT3 deficient HIES, AR-HIES lacks the connective tissue and skeletal manifestations but has an increase in neurologic abnormalities. In this review, we discuss the clinical presentations, genetic etiologies, and immunologic abnormalities of these two syndromes. In addition, we discuss animal models of STAT3 deficiency that provide insight into the pathogenesis of HIES. Further understanding of how STAT3 results in the diverse manifestations of HIES will allow us to develop more specific therapies for HIES as well as for many of the manifestations, such as scoliosis, recurrent staphylococcal infections, and eczema, which are common in the general population. (Pediatr Res 65: 32R-37R, 2009)