主导负面与功能增长的STAT3缺陷:流行病学,临床,免疫学和分子方面的系统性审查
Amirhossein Hajialigol1, Gholamreza Azizi2, Mahnaz Seifi Alan3
1Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran; Alborz Office of Universal Scientific Education and Research Network (USERN), Alborz University of Medical Sciences, Karaj, Iran.
The journal of allergy and clinical immunology. In practice
|April 17, 2025
概括
生殖系STAT3突变导致不同的综合征. 主导阴性 (DN) STAT3突变会导致感染和湿疹,而功能获取 (GOF) STAT3突变会导致早期发生的自身免疫.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 遗传学 是一个
- 临床医学 临床医学
背景情况:
- 信号转换器和转录3激活器 (STAT3) 的生殖系突变与两个不同的临床综合征有关.
- 这些综合征具有主要的传染性或自身免疫性表型.
研究的目的:
- 系统地审查和编译关于STAT3基因的功能增益 (GOF) 和主导负 (DN) 突变的现有文献.
- 分析和比较与STAT3-DN和STAT3-GOF突变相关的临床表现和免疫学概况.
主要方法:
- 在PubMed,Scopus和Web of Science数据库中进行了全面的文献搜索.
- 搜索涵盖了1990年至2023年的出版物,包括主要评论和全文文章的手动搜索.
- 分析了107篇关于490名患者的文章的数据.
主要成果:
- 在STAT3-DN (265名患者) 和STAT3-GOF (225名患者) 队列之间观察到显著的临床差异.
- 在STAT3-DN患者中,感染并发症 (98.2%),肺炎 (67.3%),鼻炎 (17.5%),耳炎 (27.7%), (52.7%) 和皮肤症状 (88.3%) 的发生率较高,IgE水平也较高.
- 在STAT3-GOF患者中,间歇性肺病 (17.7%),内分泌病 (16.5%) 和早期多重自身免疫的发病率较高,往往需要免疫抑制治疗. 淋巴细胞亚群分析揭示了不同的模式,STAT3-DN患者具有更高的CD3+T细胞和更低的NK细胞,而STAT3-GOF患者具有更低的CD4+T细胞.
结论:
- STAT3-DN突变的特点是经常性感染,湿疹,IgE升高和eosinophilia.
- STAT3-GOF突变与早期出现的多种自身免疫和经常需要免疫抑制治疗有关.
- 这些发现突出了由不同类型的生殖 STAT3 突变驱动的对比的临床表型.
相关概念视频
The JAK-STAT Signaling Pathway
8.4K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.4K
Abnormal Proliferation
4.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
Loss of Tumor Suppressor Gene Functions
4.6K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.6K
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
NF-κB-dependent Signaling Pathway
7.2K
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...
7.2K
Regulated Protein Degradation
7.1K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.1K


