Department of Genetics, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh, Saudi Arabia.
College of Public Health, Medical and Veterinary Sciences, Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia.
Allergy. 2019 Feb;74(2):370-379. doi: 10.1111/all.13610. Epub 2018 Oct 15.
Hyper-IgE syndromes (HIES) are a clinically overlapping, heterogeneous group of inborn errors of immunity characterized by elevated serum IgE level, eosinophilia, atopy, and immune dysregulation. Deficiency of DOCK8 protein is potentially a life-threatening autosomal recessive HIES and only curable with bone marrow transplantation. Hence, the diagnosis of DOCK8 deficiency is critical and should be sought at an early stage to initiate definitive therapy.
Serum samples from patients with DOCK8 deficiency and atopic dermatitis were profiled on a cytokine/chemokine panel for potential differential expression.
CXCL10 and TNF-A were upregulated in DOCK8 patients when compared to AD, possibly contributing toward increased susceptibility to infections and cancer. In contrast, epidermal growth factor (EGF) was significantly downregulated in a subgroup of DOCK8-deficient and AD patients, while IL-31 expression was comparable between both DOCK8-deficient and AD cohorts, possibly contributing toward pruritus seen in both groups.
This comprehensive cytokine profile in HIES patients reveals distinctive biomarkers that differentiate between the DOCK8-deficient and AD patients. The unique expression profile of various inflammatory cytokines in patients with DOCK8 deficiency vs atopic dermatitis likely reflects disease-specific perturbations in multiple cellular processes and pathways leading to a predisposition to infections and allergies seen in these patients. These data agree with the role for EGF replacement therapy in EGF-deficient individuals with AD as well as DOCK8 deficiency through a potential shared pathway. In addition, these novel biomarkers may be potentially useful in distinguishing DOCK8 deficiency from AD allowing early-targeted treatment options.
高免疫球蛋白 E 综合征（HIES）是一组临床重叠、异质性的先天性免疫缺陷，其特征为血清 IgE 水平升高、嗜酸性粒细胞增多、特应性和免疫失调。DOCK8 蛋白缺陷可能是一种危及生命的常染色体隐性遗传性 HIES，只能通过骨髓移植治愈。因此，DOCK8 缺陷的诊断至关重要，应尽早进行，以启动明确的治疗。
对 DOCK8 缺陷和特应性皮炎患者的血清样本进行细胞因子/趋化因子谱分析，以寻找潜在的差异表达。
与 AD 相比，DOCK8 患者的 CXCL10 和 TNF-A 上调，可能导致其更容易感染和患癌症。相比之下，表皮生长因子（EGF）在部分 DOCK8 缺陷和 AD 患者中显著下调，而 IL-31 的表达在 DOCK8 缺陷和 AD 两组间相当，可能导致两组均有瘙痒。
HIES 患者的这一全面细胞因子谱揭示了可区分 DOCK8 缺陷和 AD 患者的独特生物标志物。与特应性皮炎相比，DOCK8 缺陷患者中各种炎症细胞因子的独特表达谱可能反映了多个细胞过程和通路的疾病特异性扰动，导致这些患者易发生感染和过敏。这些数据支持 EGF 替代疗法在 AD 和 DOCK8 缺陷患者中的作用，这可能是通过潜在的共同途径实现的。此外，这些新的生物标志物可能有助于区分 DOCK8 缺陷和 AD，从而实现早期靶向治疗。
