莱尼奥利西布减少了小鼠自身免疫性淋巴增殖综合征中的淋巴增殖性疾病
Chopie Hassan1, Yolanda Ponstein1, Robert Hanssen1
1Pharming Technologies BV, Leiden, Netherlands.
概括
作为PI3Kδ抑制剂的leniolisib在小鼠模型中有效降低了淋巴增殖和自身免疫淋巴增殖综合征 (ALPS) 的关键特征. 这一发现支持leniolisib的发现.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 自免疫淋巴增殖综合征 (ALPS) 是一种先天性免疫错误 (IEI),由缺陷的FAS介导的亡标志,导致淋巴细胞增殖和CD4-/CD8-双阴性T细胞 (DNT) 的扩张.
- 在ALPS-FAS中,DNTs在酸酸3-激酶 δ (PI3Kδ) /哺乳动物目标的拉巴胺素 (mTOR) 途径中显示出较高的活性.
- 目前的mTOR抑制剂,如西罗,显示出有效性,但需要监测,并有不良事件限制长期使用.
研究的目的:
- 为了评估leniolisib,选择性PI3Kδ抑制剂的疗效,在自身免疫淋巴增殖综合征 (ALPS) 的小鼠模型中.
- 评估leniolisib对ALPS关键特征的影响,包括淋巴增殖和免疫细胞子集.
主要方法:
- 作为ALPS的一个模型的MRL/lpr-/-小鼠通过口腔 gavage用载体或leniolisib (40或80 mg/kg/天) 接受治疗.
- 评估了器官重量的变化 (淋巴腺病变,壮病) 和免疫细胞群,特别是DNTs.
- 分析了莱尼奥利西布的剂量依赖性影响.
主要成果:
- 列尼奥利西布显著限制了淋巴腺病变和腹壮成,以剂量依赖的方式.
- CD4-/CD8-双阴性T细胞 (DNTs) 的扩张因剂量而异,通过leniolisib减少.
- 在小鼠模型中,leniolisib在减轻ALPS的正规特征方面表现出有效性.
结论:
- 用leniolisib选择性抑制PI3Kδ显示出治疗自身免疫淋巴增殖综合征 (ALPS) 的前景.
- 这些临床前发现支持ALPS患者中正在进行的leniolisib临床评估 (NCT06549114).
相关概念视频
Autoimmune Disorders
1.7K
Autoimmune diseases are a group of disorders in which the body's immune system mistakenly attacks its own cells, tissues, and organs. This results from an overactive immune response against substances and tissues normally present in the body. Let's delve into the concept and mechanism of autoimmune diseases from an immune system point of view, explore different causes and examples of such diseases, and discuss potential solutions.
Concept and Mechanism of Autoimmune Diseases
The immune...
Concept and Mechanism of Autoimmune Diseases
The immune...
1.7K
Reducing Line Loss
385
In a three-phase circuit, line loss is an indicator of energy dissipated as heat due to the resistance of transmission lines. To address this, incorporating transformers into the system—a step-up transformer at the source and a step-down transformer at the load—is a strategic solution. Two three-phase transformers are introduced to improve this.
With a step-up transformer at the source, the voltage is increased, thereby reducing the current in the transmission lines since power loss in...
With a step-up transformer at the source, the voltage is increased, thereby reducing the current in the transmission lines since power loss in...
385
Methods of reducing fever
1.4K
The signs and symptoms of fever include hot and dry skin, flushed face, thirst, muscle aches, anorexia, headache, tachycardia, tachypnea, and fatigue. Elevated body temperature is reduced using two methods: pharmacological and nonpharmacological. Proper identification and treatment of the root cause of a fever is of utmost importance.
Pharmacological Methods of Reducing Fever:
Pharmacological Methods of Reducing Fever:
1.4K
Nephrotic Syndrome I : Introduction
623
Nephrotic Syndrome is a chronic kidney disorder defined by clinical findings such as severe proteinuria, hypoalbuminemia, hyperlipidemia, and edema. These symptoms result from damage to the glomeruli, the kidney’s filtering units, increasing their permeability to proteins.Definition and Meaning:Proteinuria, defined as the loss of more than 3.5 grams of protein per day in adults, is a crucial feature of nephrotic syndrome. This condition is often accompanied by edema, the accumulation of...
623
Acute Coronary Syndrome I: Introduction
958
Acute Coronary Syndrome (ACS) encompasses a spectrum of heart conditions caused by sudden obstruction of coronary arteries, typically resulting from the rupture of an atherosclerotic plaque and subsequent thrombus (blood clot) formation. This obstruction can lead to partial or complete blockage of blood flow, causing varying degrees of myocardial ischemia or infarction.ACS includes the following clinical entities:Unstable Angina (UA)Non-ST-Elevation Myocardial Infarction (NSTEMI)ST-Elevation...
958
Adaptations that Reduce Water Loss
28.1K
Though evaporation from plant leaves drives transpiration, it also results in loss of water. Because water is critical for photosynthetic reactions and other cellular processes, evolutionary pressures on plants in different environments have driven the acquisition of adaptations that reduce water loss.
28.1K


