Sutanto Henry, Adytia Galih Januar, Fetarayani Deasy
Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia.
Curr Allergy Asthma Rep. 2025 Mar 14;25(1):17. doi: 10.1007/s11882-025-01196-8.
It seeks to answer key questions about the molecular and cellular mechanisms underlying Hyper IgE Syndrome (HIES), the genetic mutations responsible, and their contributions to both immunodeficiency and allergic manifestations. Additionally, it aims to explore diagnostic strategies and therapeutic approaches that address these overlapping domains, thereby improving disease management.
Recent research has identified several pivotal genetic mutations, including those in STAT3, DOCK8, and PGM3, which play critical roles in disrupting immune pathways such as Th17 differentiation and IgE regulation. These molecular defects have been linked to the hallmark features of HIES, including recurrent infections and elevated serum IgE levels, as well as its overlap with atopic conditions like eczema, asthma, and food allergies. Advances in diagnostic tools, such as biomarker identification and genetic testing, have improved the differentiation of HIES from more common atopic disorders. Therapeutic advancements, including the use of targeted biologics and interventions addressing both immunodeficiency and allergic symptoms, have shown promise in enhancing patient outcomes. This review highlights the role of specific genetic mutations in shaping the clinical and immunological phenotype of HIES. Key takeaways include the necessity of integrating molecular insights with clinical observations for accurate diagnosis and the potential of emerging targeted therapies to address both immunological and allergic aspects of the syndrome.
旨在回答有关高免疫球蛋白E综合征（HIES）潜在分子和细胞机制、相关基因突变及其对免疫缺陷和过敏表现的影响的关键问题。此外，旨在探索针对这些重叠领域的诊断策略和治疗方法，从而改善疾病管理。
近期研究已确定了几种关键基因突变，包括信号转导子和转录激活子3（STAT3）、细胞分裂周期蛋白42鸟嘌呤核苷酸交换因子8（DOCK8）和磷酸葡萄糖变位酶3（PGM3）中的突变，这些突变在破坏免疫途径（如辅助性T细胞17（Th17）分化和免疫球蛋白E（IgE）调节）中起关键作用。这些分子缺陷与HIES的标志性特征有关，包括反复感染和血清IgE水平升高，以及它与湿疹、哮喘和食物过敏等特应性疾病的重叠。诊断工具的进展，如生物标志物识别和基因检测，改善了HIES与更常见特应性疾病的鉴别。治疗进展，包括使用靶向生物制剂以及针对免疫缺陷和过敏症状的干预措施，在改善患者预后方面显示出前景。本综述强调了特定基因突变在塑造HIES临床和免疫表型中的作用。关键要点包括将分子见解与临床观察相结合以进行准确诊断的必要性，以及新兴靶向治疗解决该综合征免疫和过敏方面问题的潜力。
