Somatic STAT3 Gain-of-Function (GOF) syndrome underlying susceptibility to Parvovirus B19, Pseudomonas aeruginosa, and Histoplasma capsulatum infections

Q3 Medicine
Cedric Julien , Stephane Bernier , Denis Cournoyer , Yichun Sun , Anna Perez , Joy Agbonze , Isabelle Angers , Lucie Roussel , Gizelle Popradi , Donald C. Vinh
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引用次数: 0

Abstract

Infections in overtly immunocompromised persons (e.g. those living with advanced HIV, receiving malignancy-targeting chemotherapy, or recipients of transplants), may present with severe disease. In the absence of overt immunosuppression, unexplained severe disease due to prevalent microbes may reflect an underlying “inborn error of immunity” (IEI). IEI are monogenic penetrant defects of immunity: Classically, the genetic mutation is germline, that is, derived from germ cells, vertically transmitted to offspring in Mendelian fashion (autosomal dominant, autosomal recessive, or X-linked), and present in all cells of the affected individual. IEI may also be caused by naturally-occurring autoantibodies directed to immunologic components (such as cytokines) (Casanova et al., 2024) or by somatic mutations (Aluri and Cooper, 2023). Somatic mutations occur when a deleterious genetic variant occurs in the post-zygotic stage of development and can affect any body cell, other than germ cells; they are well-known causes of solid and hematologic malignancies. Somatic IEI syndromes are emerging, typically associated with lymphoproliferative diseases or autoinflammatory disorders. We report the case of a young woman with unexplained severe infections in whom a somatic gain-of-function (GOF) mutation in Signal transducer and activator of transcription 3 (STAT3) was found.
体细胞 STAT3 功能增益 (GOF) 综合征是 Parvovirus B19、铜绿假单胞菌和荚膜组织胞浆菌感染易感性的基础
免疫力明显低下的人(如晚期艾滋病毒感染者、接受恶性肿瘤靶向化疗者或接受移植者)感染后可能会出现严重的疾病。在没有明显免疫抑制的情况下,由流行微生物引起的原因不明的严重疾病可能反映了潜在的 "先天性免疫错误"(IEI)。先天性免疫缺陷是一种单基因渗透性免疫缺陷:一般来说,基因突变是生殖性的,即来自生殖细胞,以孟德尔方式垂直传递给后代(常染色体显性、常染色体隐性或 X 连锁),并存在于受影响个体的所有细胞中。IEI 也可能由针对免疫成分(如细胞因子)的天然自身抗体(Casanova 等人,2024 年)或体细胞突变(Aluri 和 Cooper,2023 年)引起。体细胞突变是指有害的基因变异发生在后染色体发育阶段,可影响生殖细胞以外的任何体细胞;体细胞突变是众所周知的实体瘤和血液系统恶性肿瘤的病因。体细胞 IEI 综合征正在出现,通常与淋巴组织增生性疾病或自身炎症性疾病相关。我们报告了一例年轻女性不明原因的严重感染病例,在她体内发现了信号转导和激活转录 3(STAT3)的体细胞功能增益(GOF)突变。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical Infection in Practice
Clinical Infection in Practice Medicine-Infectious Diseases
CiteScore
2.10
自引率
0.00%
发文量
95
审稿时长
82 days
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