Combined Immunodeficiency in Patients With Trichohepatoenteric Syndrome.
Combined Immunodeficiency in Patients With Trichohepatoenteric Syndrome.
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DOI：
10.3389/fimmu.2018.01036
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发表时间：
2018
影响因子：
7.3
通讯作者：
Fabre A
中科院分区：
文献类型：
--
作者：
Vély F;Barlogis V;Marinier E;Coste ME;Dubern B;Dugelay E;Lemale J;Martinez-Vinson C;Peretti N;Perry A;Bourgeois P;Badens C;Goulet O;Hugot JP;Farnarier C;Fabre A
综合征性腹泻/毛肝肠综合征 (SD/THE) 是一种罕见的多系统遗传性疾病，由 SKIV2L 或 TTC37 突变引起，这两个基因编码参与 RNA 降解的假定人类 SKI 复合体的亚基。主要特征是婴儿顽固性腹泻、毛发异常、面部畸形、宫内生长受限。从免疫学角度来说，这种综合征与导致免疫球蛋白补充的低丙种球蛋白血症有关。我们对法国一大群 SD/THE 患者的免疫评估发现了一些免疫学缺陷。首先，转换记忆B淋巴细胞计数非常低。其次，T 细胞和 NK 细胞产生的 IFN-γ 受到损害，并与 NK 细胞脱颗粒减少有关。第三，3/6 TTC37 突变患者的 T 细胞增殖异常。这三名患者均出现严重的 EBV 感染和短暂的噬血细胞增多症，这可能与这些免疫缺陷有关。此外，对具有 SD/THE 临床特征的患者进行免疫学筛查可以促进这些患者的诊断和治疗管理。
The syndromic diarrhea/trichohepatoenteric syndrome (SD/THE) is a rare and multi-system genetic disorder caused by mutation in SKIV2L or in TTC37, two genes encoding subunits of the putative human SKI complex involved in RNA degradation. The main features are intractable diarrhea of infancy, hair abnormalities, facial dysmorphism, and intrauterine growth restriction. Immunologically this syndrome is associated with a hypogammaglobulinemia leading to an immunoglobulin supplementation. Our immune evaluation of a large French cohort of SD/THE patient revealed several immunological defects. First, switched memory B lymphocytes count is very low. Second, IFN-γ production by T and NK cells is impaired and associated with a reduced degranulation of NK cells. Third, T cell proliferation was abnormal in 3/6 TTC37-mutated patients. These three patients present with severe EBV infection and a transient hemophagocytosis which may be related to these immunological defects. Moreover, an immunological screening of patients with clinical features of SD/THE could facilitate both diagnosis and therapeutic management of these patients.