IFIH1功能丧失导致炎症和与SARS-CoV-2相关的传染病的发生
Rania Najm1, Lemis Yavuz2, Ruchi Jain3
1College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai, United Arab Emirates.
Scandinavian journal of immunology
|May 17, 2024
概括
编码黑色素瘤分化相关蛋白5 (MDA5) 的IFIH1基因的罕见变异可能导致严重的免疫缺陷. 这些遗传变化使个体易患感染和炎症,包括COVID-19和MIS-C.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 传染性疾病 传染性疾病
背景情况:
- IFIH1基因编码黑色素瘤分化相关蛋白5 (MDA5),这是检测病毒感染的先天免疫的关键调节者.
- MDA5的失调与免疫力减弱,感染易感性增加和自身免疫性疾病有关.
- 功能增强的IFIH1变体会导致艾卡迪-古蒂埃尔和辛格尔顿-默顿综合征;功能丧失会导致免疫缺陷.
研究的目的:
- 研究IFIH1功能丧失变体在患有复发性感染,炎症性疾病,严重COVID-19或儿童多系统炎症综合征 (MIS-C) 的患者中的作用.
主要方法:
- 整体外体序列测序用于识别9名受影响患者的假定功能丧失的IFIH1变体.
- 分析了临床数据,包括炎症标志物 (CRP,粉样蛋白A,费里丁,IL-6) 和淋巴缺血症.
- 在Poly (I:C) 刺激后进行了外周血液单核细胞 (PBMC) 表达分析,以评估免疫应答中断.
主要成果:
- 确定了9名患有假定功能丧失的IFIH1变体的患者,出现淋巴缺血症和炎症标志物升高.
- 特定变种 (c.2807+1G>A,c.1641+1G>C,c.2016delA) 与严重的免疫缺陷,血球炎,周期性发烧,COVID-19,MIS-C和炎症性肠病有关.
- 在男性中,IFIH1单基因功能丧失和感染易感性之间发现了显著的关联.
- PBMC表达分析显示,患有c.2016delA变异的患者的ISG15,IFNA和IFNG转录水平下降,表明免疫反应受损.
结论:
- 罕见的,单一的IFIH1功能丧失变体显著改变免疫反应.
- 这些变种严重使个人易患炎症和传染病,包括与SARS-CoV-2相关的疾病.
更多相关视频
09:56Intra-tracheal Administration of Haemophilus influenzae in Mouse Models to Study Airway Inflammation
Published on: March 2, 2016
10.3K
10:00High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
13.4K
相关概念视频
Immunodeficiency Diseases
936
Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency...
There are three main causes of immunodeficiency...
936
Factors Affecting the Risk of Infection
11.8K
The hosts' susceptibility to infection depends on several factors. The integrity of the skin and mucous membranes helps protect the body against microbial attacks. When the skin is altered, the chance of infection, limb loss, and even death increases.
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin...
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin...
11.8K
NF-κB-dependent Signaling Pathway
7.4K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.4K
Single Nucleotide Polymorphisms-SNPs
15.0K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.0K
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
