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首页> 外文期刊>Nature immunology >Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency
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Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency

机译：遗传性HOIL-1和LUBAC缺乏症的人的免疫缺陷，自身炎症和支链淀粉病

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摘要

We report the clinical description and molecular dissection of a new fatal human inherited disorder characterized by chronic autoinflammation, invasive bacterial infections and muscular amylopectinosis. Patients from two kindreds carried biallelic loss-of-expression and loss-of-function mutations in HOIL1 (RBCK1), a component of the linear ubiquitination chain assembly complex (LUBAC). These mutations resulted in impairment of LUBAC stability. NF-κB activation in response to interleukin 1β (IL-1β) was compromised in the patients' fibroblasts. By contrast, the patients' mononuclear leukocytes, particularly monocytes, were hyper-responsive to IL-1β. The consequences of human HOIL-1 and LUBAC deficiencies for IL-1β responses thus differed between cell types, consistent with the unique association of autoinflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-κB-dependent IL-1β responses differently in different cell types.
机译：我们报告了一种新的致命人类遗传性疾病的临床描述和分子解剖，该疾病以慢性自发性炎症，侵袭性细菌感染和肌支链淀粉样变性为特征。来自两个亲戚的患者在线性泛素化链装配复合体（LUBAC）的一个组成部分HOIL1（RBCK1）中携带双等位基因表达缺失和功能丧失突变。这些突变导致LUBAC稳定性受损。在患者的成纤维细胞中，对白介素1β（IL-1β）响应的NF-κB激活受到损害。相比之下，患者的单核白细胞，特别是单核细胞对IL-1β敏感。因此，人类HOIL-1和LUBAC缺乏对IL-1β反应的后果在细胞类型之间是不同的，这与这些患者自身炎症和免疫缺陷的独特关联相一致。这些数据表明LUBAC在不同的细胞类型中调节NF-κB依赖的IL-1β反应不同。

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