遗传性人类 ZNF341 缺乏症。
Inherited human ZNF341 deficiency.
机构信息
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University of Paris Cité, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
Clinical Immunology Department, Saint Louis Hospital, AP-HP de Paris University of Paris, Paris, France; Department of Clinical Immunology, University of Paris Cité, Assistance Publique Hôpitaux de Paris (AP-HP), Saint-Louis Hospital, Paris, France.
出版信息
Curr Opin Immunol. 2023 Jun;82:102326. doi: 10.1016/j.coi.2023.102326. Epub 2023 Apr 18.
Typical hyper-IgE syndromes (HIES) are caused by autosomal-dominant-negative (DN) variants of STAT3 (Signal Transducer And Activator Of Transcription 3) or IL6ST (Interleukin 6 Cytokine Family Signal Transducer), biallelic partial loss-of-function (LOF) variants of IL6ST, or biallelic complete LOF variants of ZNF341 (Zinc Finger Protein 341). Including the two new cases described in this review, only 20 patients with autosomal-recessive (AR) ZNF341 deficiency have ever been reported. Patients with AR ZNF341 deficiency have clinical and immunological phenotypes resembling those of patients with autosomal-dominant STAT3 deficiency, but with a usually milder clinical presentation and lower NK (Natural Killer) cell counts. ZNF341-deficient cells have 50% the normal level of STAT3 in the resting state. However, as there is no clear evidence that STAT3 haploinsufficiency causes HIES, this decrease alone is probably insufficient to explain the HIES phenotype observed in the ZNF341-deficient patients. The combination of decreased basal expression level and impaired autoinduction of STAT3 observed in ZNF341-deficient lymphocytes is considered a more likely pathophysiological mechanism. We review here what is currently known about the ZNF341 gene and ZNF341 deficiency, and briefly discuss possible roles for this protein in addition to its control of STAT3 activity.
典型的高免疫球蛋白 E 综合征（HIES）是由 STAT3（信号转导和转录激活因子 3）或 IL6ST（白细胞介素 6 细胞因子家族信号转导）的常染色体显性负（DN）变异体、IL6ST 的双等位基因部分功能丧失（LOF）变异体或 ZNF341（锌指蛋白 341）的双等位基因完全 LOF 变异体引起的。包括本综述中描述的两个新病例，仅有 20 例常染色体隐性（AR）ZNF341 缺乏症患者被报道过。AR ZNF341 缺乏症患者具有类似于常染色体显性 STAT3 缺乏症患者的临床和免疫学表型，但临床表现通常较轻，NK（自然杀伤）细胞计数较低。在静息状态下，ZNF341 缺陷细胞的 STAT3 水平为正常水平的 50%。然而，由于没有明确的证据表明 STAT3 杂合不足会导致 HIES，因此这种下降本身可能不足以解释 ZNF341 缺陷患者中观察到的 HIES 表型。在 ZNF341 缺陷的淋巴细胞中观察到的基础表达水平降低和 STAT3 自身诱导受损的组合被认为是一种更可能的病理生理机制。我们在这里回顾了目前已知的 ZNF341 基因和 ZNF341 缺乏症，并简要讨论了除了控制 STAT3 活性之外，该蛋白可能具有的作用。
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