AlYafie Randa, Velayutham Dinesh, van Panhuys Nicholas, Jithesh Puthen Veettil
College of Health and Life Sciences, Hamad bin Khalifa University, Doha, Qatar.
Laboratory of Immunoregulation, Research Department, Sidra Medicine, Doha, Qatar.
Front Immunol. 2025 Feb 18;16:1516068. doi: 10.3389/fimmu.2025.1516068. eCollection 2025.
Hyper IgE syndromes (HIES) form a rare group of primary immunodeficiency disorders (PIDs) distinguished by persistent skin abscesses, dermatitis, allergies, and infections, in addition to their characteristic high serum IgE levels. Autosomal dominant (AD) and autosomal recessive (AR) genetic defects have been reported in HIES. From a clinical perspective, AD-HIES cases generally exhibit several non-immunologic features, including connective tissue, dental and skeletal abnormalities, whilst AR-HIES conditions have a higher incidence of neurologic complications and cutaneous viral infections. Genetic defects associated with HIES lead to impaired immune signaling, affecting pathways crucial for immune cell development, function, and immune response to pathogens/allergens. As a result, HIES patients are predisposed to recurrent bacterial and/or fungal infections, as well as atopic allergic responses. In many cases, the exact biological mechanisms responsible for the variations observed in the clinical phenotypes between the two inherited forms of HIES are still unclear. In this review, we describe the genetic basis of HIES with a distinction between the AR-HIES and AD-HIES forms, to better comprehend the different underlying molecular mechanisms, a distinction which is imperative for the accurate diagnosis, management, and development of targeted therapies for HIES patients.
高IgE综合征（HIES）是一组罕见的原发性免疫缺陷疾病（PID），其特征除了血清IgE水平持续升高外，还包括持续性皮肤脓肿、皮炎、过敏和感染。HIES已报道有常染色体显性（AD）和常染色体隐性（AR）遗传缺陷。从临床角度来看，AD-HIES病例通常表现出几种非免疫特征，包括结缔组织、牙齿和骨骼异常，而AR-HIES疾病的神经并发症和皮肤病毒感染发生率更高。与HIES相关的遗传缺陷导致免疫信号受损，影响对免疫细胞发育、功能以及对病原体/过敏原免疫反应至关重要的信号通路。因此，HIES患者易发生复发性细菌和/或真菌感染以及特应性过敏反应。在许多情况下，导致两种遗传形式的HIES临床表型出现差异的确切生物学机制仍不清楚。在本综述中，我们描述了HIES的遗传基础，并区分了AR-HIES和AD-HIES形式，以便更好地理解不同的潜在分子机制，这种区分对于准确诊断、管理和开发针对HIES患者的靶向治疗至关重要。
