在非典型的血溶性尿素性综合征中,与H因子相关蛋白5的遗传变异相关的补充失调
Sigridur Sunna Aradottir1, Ann-Charlotte Kristoffersson1, Erik Linnér1
1Department of Pediatrics, Clinical Sciences Lund, Lund University, 22185, Lund, Sweden.
Pediatric nephrology (Berlin, Germany)
|November 13, 2023
概括
一个儿童的非典型血溶性尿性综合征 (aHUS) 与CFHR5遗传变异有关. 由于分泌量下降,H因子相关蛋白5 (FHR5) 的低水平可能会导致补充激活和aHUS的发展.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 遗传学 是一个遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- 非典型的血溶性尿素综合征 (aHUS) 是一种罕见的疾病,通常与影响补体调节的遗传因素有关.
- 与H因子相关 (FHR) 蛋白质的突变或缺失与aHUS.US的致病性有关.
- 与H因子相关的蛋白5 (FHR5) 在补体系统调节中起作用.
研究的目的:
- 在儿科患者中调查aHUS的遗传和分子基础.
- 评估新型CFHR5变异对FHR5水平和补充活性的功能影响.
- 探索FHR5缺乏对aHUS病变发生的潜在贡献.
主要方法:
- 进行了包括桑格和下一代测序在内的遗传分析.
- 血清FHR5水平使用免疫栓塞和ELISA进行评估.
- 功能性测试包括测量子红细胞血解在患者血清和复合FHR5.5的存在下.
- 在HEK细胞中进行了变异性研究,以评估蛋白质表达和分泌.
主要成果:
- 一名患有aHUS的儿童呈现出异体CFHR5 M514R变异,同体CFHR3/CFHR1缺失,抗H因子抗体和低C3水平.
- 患者血清显示FHR5水平降低,并诱导子红细胞的血液溶解,通过添加复合FHR5.5减弱.
- 在CFHR5 M514R变体中,HEK细胞的分泌受损,导致细胞内积累.
结论:
- CFHR5 M514R变体与FHR5分泌量下降有关,这可能解释了患者的低血清FHR5水平.
- 降低FHR5水平可能会损害红细胞的补体调节,从而导致aHUS的发展.
- 这些发现突出了一个涉及FHR5缺乏症在aHUS病理生理学中的新机制.
相关概念视频
Complement System
2.4K
The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
2.4K
Complementation Tests
4.9K
A complementation test is a simple cross to identify whether the two mutations are located on the same gene or different genes. It was first performed by Edward Lewis in the 1940s while working on fruit flies. He developed the test to identify the location and arrangement of different mutations on chromosomes.
Organisms heterozygous for different mutations are crossed pairwise in all combinations. If present on different genes, the mutations can complement each other by providing the missing...
Organisms heterozygous for different mutations are crossed pairwise in all combinations. If present on different genes, the mutations can complement each other by providing the missing...
4.9K
Disorders of Hemostasis
957
Hemostasis, the process that stops bleeding after a blood vessel injury, is crucial for maintaining the integrity of the circulatory system. However, disorders of hemostasis can disrupt this delicate balance, leading to either excessive clotting or bleeding. These disorders can be broadly classified into thromboembolic disorders and bleeding disorders.
Thromboembolic Disorders
Two factors primarily cause thromboembolic conditions.
Thromboembolic Disorders
Two factors primarily cause thromboembolic conditions.
957
Anticoagulant Drugs: Low-Molecular-Weight Heparins
719
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
719
Humoral Immune Responses
72.8K
Overview
72.8K
Multiple Allele Traits
34.3K
The Concept of Multiple Allelism
34.3K


