In-depth immune profiling of a patient with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2 caused by a novel mutation in ZBTB24.

IF 3.4 3区 医学 Q3 IMMUNOLOGY
Colleen M Roark, Diana Ramírez-Vásquez, Jenniffer Yissel Giron Martinez, Xin Zhen, Alexa N Del Bene, Shannon E Gibson, Megan Dobrose, Natasha B Halasa, Lizbeth Blancas-Galicia, Ruben Martinez-Barricarte
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引用次数: 0

Abstract

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare genetic disorder characterized by immunodeficiency and chromosomal instability. Mutations in DNA methylation genes such as DNMT3B (ICF1), ZBTB24 (ICF2), CDCA7 (ICF3), and HELLS (ICF4) cause ICF. ICF2 syndrome has been previously described, yet the extent of its clinical presentation and immunological consequences needs to be further elucidated. We describe a patient with a novel homozygous mutation in ZBTB24 (Q375Hfs*3). While infections with extracellular pathogens are frequent in other reported ICF2 patients, our patient also displays infections by intracellular pathogens. At the molecular level, we showed that the novel mutation results in a truncated ZBTB24 protein that disrupts its function in DNA methylation. We thoroughly characterized the immunological consequences of ZBTB24 deficiency using mass cytometry coupled with state-of-the-art computational methods. Our analysis revealed reduced frequencies of natural killer cells and class-switched memory B cell populations in our patient, along with low levels of the immunoglobulin isotypes IgG4 and IgM. Despite observing normal cell frequencies within the T and myeloid compartments, the clinical presentation of this patient suggests a functional defect in immune cells known to be critical to combat intracellular pathogens. Overall, this study expands the clinical and immunological features of ZBTB24 deficiency and highlights the importance of ZBTB24 to the human immune response.

1例由ZBTB24基因突变引起的免疫缺陷、着丝粒不稳定和2型面部异常综合征患者的深入免疫分析
免疫缺陷、着丝粒不稳定及面部异常(ICF)综合征是一种罕见的以免疫缺陷和染色体不稳定为特征的遗传性疾病。DNA甲基化基因如DNMT3B (ICF1)、ZBTB24 (ICF2)、CDCA7 (ICF3)和HELLS (ICF4)的突变导致ICF。ICF2综合征此前已有报道,但其临床表现和免疫学后果的程度有待进一步阐明。我们描述了一例ZBTB24基因(Q375Hfs*3)发生新型纯合突变的患者。虽然细胞外病原体感染在其他报告的ICF2患者中很常见,但我们的患者也表现出细胞内病原体感染。在分子水平上,我们发现这种新的突变导致ZBTB24蛋白被截断,破坏了它在DNA甲基化中的功能。我们使用细胞计数技术结合最先进的计算方法彻底表征了ZBTB24缺乏的免疫学后果。我们的分析显示,患者的自然杀伤细胞和类别转换记忆B细胞群的频率降低,免疫球蛋白同种型IgG4和IgM的水平也较低。尽管观察到T细胞和髓细胞间室的正常细胞频率,但该患者的临床表现表明,免疫细胞的功能缺陷是对抗细胞内病原体的关键。总之,本研究拓展了ZBTB24缺乏症的临床和免疫学特点,突出了ZBTB24对人体免疫应答的重要性。
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
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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