Department of Clinical and Experimental Medicine, "Angelo Nocivelli" Institute for Molecular Medicine, University of Brescia, Italy.
Laboratory of Genetic Disorders of Childhood, "Angelo Nocivelli" Institute for Molecular Medicine, Spedali Civili of Brescia, Brescia, Italy.
Clin Immunol. 2014 May-Jun;152(1-2):164-70. doi: 10.1016/j.clim.2014.03.008. Epub 2014 Mar 24.
Hyper-IgE syndrome (HIES) is a genetic disorder characterized by elevated IgE serum levels, mostly due to mutations in STAT3 or DOCK8. Despite clinical heterogeneity between the two forms of the disease, clinical manifestations may not be conclusive for diagnosis and immunological differences are still unclear. Herein, we performed a detailed characterization of the T- and B-cell compartments by flow cytometry in seven HIES patients with homozygous DOCK8 mutations and six patients presenting heterozygous STAT3 mutations. We observed that DOCK8-deficient patients showed a marked reduction of naive and recent thymic emigrant (RTE) T lymphocytes together with a relative increase of activated T cells, most of which co-expressed the chemokine receptor CCR4, a marker of Th2 polarization. Moreover, an extreme reduction of memory B cells was detected, despite a normal/increased proportion of immunoglobulin-secreting cells. These observations indicate that DOCK8-deficient patients display a distinctive immunophenotype which is characteristic of this form of HIES.
高免疫球蛋白 E 综合征（HIES）是一种遗传性疾病，其特征是血清 IgE 水平升高，主要归因于 STAT3 或 DOCK8 的突变。尽管两种形式的疾病在临床表现上存在异质性，但诊断并不明确，免疫差异仍不清楚。在此，我们通过流式细胞术对 7 名 DOCK8 基因突变纯合子 HIES 患者和 6 名 STAT3 基因突变杂合子患者的 T 细胞和 B 细胞进行了详细特征描述。我们发现 DOCK8 缺陷患者的幼稚 T 细胞和近期胸腺迁出（RTE）T 淋巴细胞明显减少，同时激活的 T 细胞相对增加，其中大多数共表达趋化因子受体 CCR4，这是 Th2 极化的标志。此外，还检测到记忆 B 细胞极度减少，尽管免疫球蛋白分泌细胞的比例正常/增加。这些观察结果表明，DOCK8 缺陷患者表现出独特的免疫表型，这是这种形式的 HIES 的特征。
