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    • 3. 发明申请
    • INFLAMMATORY DISEASE DIAGNOSIS AND METHODS OF TREATMENT USING LIPOPOLYSACCHARIDES-RESPONSIVE BEIGE-LIKE ANCHOR
    • 炎症性疾病诊断和使用脂多糖拮抗剂类似锚的治疗方法
    • US20160108108A1
    • 2016-04-21
    • US14223490
    • 2014-03-24
    • Jia-Wang WangRichard F. Lockey
    • Jia-Wang WangRichard F. Lockey
    • C07K16/18A61K38/05C12N15/113A61K38/17
    • C07K16/18A61K31/69A61K31/713A61K35/16A61K38/1709A61K45/06A61K2039/505C07K14/4702C07K14/4713C07K2317/76C12N15/113C12N2310/14C12N2310/141C12N2310/531C12N2330/10C12N2330/50A61K2300/00
    • Anti-cytokine therapy has revolutionized immunological disease treatment, but is not always effective and subject to treatment resistance as the cytokine cascade is highly redundant and multiple cytokines are involved in inflammation. Targeting a critical common regulator of inflammatory effectors is desirable. Lipopolysaccharide (LPS)-responsive beige-like anchor (LRBA) is a master regulator of multiple genes important for inflammation. Subcellular localization shows that LRBA translocated to the nucleus upon LPS stimulation and colocalized with multiple proteins associated with the endosome membrane system, indicating a critical role in membrane/vesicle trafficking essential for deposition, secretion and signal transduction of immune effectors. Deregulation, deficiency, down-regulation and overexpression of LRBA causes defective trafficking and signaling of immune effector molecules, resulting in immunodeficiency and autoimmunity diseases associated with a broader spectrum of severe symptoms when compared to other CVID genes. Modulating LRBA through antibodies, dominant negative mutants, or small interference RNA can be used to treat inflammatory diseases.
    • 抗细胞因子治疗已经彻底革新了免疫疾病的治疗,但并不总是有效的,并且受到治疗抗性,因为细胞因子级联是高度冗余的,并且多种细胞因子参与炎症。 靶向炎症反应的关键共同调节剂是可取的。 脂多糖(LPS) - 反应性米色样锚(LRBA)是对炎症重要的多种基因的主要调节剂。 亚细胞定位显示,LPS刺激后,LRBA转移到细胞核,并与多个与内膜膜系统相关的蛋白质共定位,表明在免疫作用子的沉积,分泌和信号传导所必需的膜/囊泡运输中起关键作用。 与其他CVID基因相比,LRBA的放松,缺乏,下调和过表达导致免疫效应分子的不良运输和信号转导,导致与广泛的严重症状相关的免疫缺陷和自身免疫疾病。 通过抗体,显性负突变体或小干扰RNA调节LRBA可用于治疗炎症性疾病。