Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Pediatr Allergy Immunol. 2019 Jun;30(4):469-478. doi: 10.1111/pai.13043. Epub 2019 May 15.
Hyper-IgE syndromes (HIES) are distinct diseases characterized by recurrent cutaneous and lung infections, eczema, and elevated serum IgE level.
In this study, clinical manifestations, immunologic findings, and genetic studies of all patients with HIES in the Iranian national registry database were evaluated.
A total of 129 HIES patients with a median age of 14.0 (9.0-24.0) years were followed up for a total of 307.8 patient-years. Genetic studies showed heterozygous STAT3 mutations in 19 patients and homozygous DOCK8 mutation in 16 patients. The mean of National Institutes of Health score in STAT3-deficient patients was higher than in patients with DOCK8 mutation (P = 0.001). It was shown that the presence of pneumatocele and hematologic complication were significantly frequent in STAT3-deficient cases compared to patients with DOCK8 deficiency (P = 0.001 and P = 0.002, respectively). Moreover, the median IgE serum levels were higher in patients with STAT3 gene mutation than in patients with DOCK8 gene mutation (P = 0.02). The eosinophils' count was enhanced in patients with DOCK8 deficiency than in patients with STAT3 gene defects (P = 0.02).
Specific molecular study of STAT3 and DOCK8 mutations in patients with HIES clinical phenotype could help the physician to definitively characterize the disease. Since HIES showed the highest rate of unsolved combined immunodeficiency, investigation of other genetic and environmental factors could also help in understanding the mechanism of remaining patients as well as providing strategy into therapeutic modalities.
高免疫球蛋白 E 综合征（HIES）是一组以复发性皮肤和肺部感染、特应性皮炎和血清 IgE 水平升高为特征的疾病。
本研究评估了伊朗国家登记数据库中所有 HIES 患者的临床表现、免疫学发现和遗传学研究。
共随访了 129 例 HIES 患者，中位年龄为 14.0（9.0-24.0）岁，总随访时间为 307.8 患者年。遗传研究显示 19 例患者存在 STAT3 杂合突变，16 例患者存在 DOCK8 纯合突变。STAT3 缺陷患者的 NIH 评分均值高于 DOCK8 突变患者（P=0.001）。与 DOCK8 缺陷患者相比，STAT3 缺陷患者的肺大疱和血液学并发症更常见（P=0.001 和 P=0.002）。此外，STAT3 基因突变患者的血清 IgE 水平中位数高于 DOCK8 基因突变患者（P=0.02）。与 STAT3 基因突变患者相比，DOCK8 基因突变患者的嗜酸性粒细胞计数更高（P=0.02）。
对具有 HIES 临床表型的患者进行 STAT3 和 DOCK8 突变的特异性分子研究，可以帮助医生明确疾病的特征。由于 HIES 表现出最高的未解决联合免疫缺陷发生率，对其他遗传和环境因素的研究也有助于了解其余患者的发病机制，并为治疗方式提供策略。
