Targeted strategies directed at the molecular defect: Toward precision medicine for select primary immunodeficiency disorders.
Targeted strategies directed at the molecular defect: Toward precision medicine for select primary immunodeficiency disorders.
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DOI：
10.1016/j.jaci.2017.01.004
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Fleisher TA
中科院分区：
文献类型：
--
作者：
Notarangelo LD;Fleisher TA
原发免疫缺陷疾病(PID)是一系列由基因决定的疾病，通常会增加感染的易感性，在许多疾病中也有免疫调节失调的证据，通常表现为自身免疫。最近，与ID相关的功能获得(GOF)突变的概念已经得到很好的认识，并为理解这组疾病增加了一个新的维度，超越了更常见的功能突变丧失。在以前没有特征性的遗传缺陷中发现的迅速扩大的遗传缺陷，为针对特定致病异常的靶向治疗打开了可能性。这是通过将特定于PID的遗传缺陷与可接受定向治疗的细胞信号通路中相关的独特异常联系起来。这些药物包括过度阻断活性或在反应细胞通路下增强的药物。选择了选定的初级免疫缺陷，其遗传缺陷最近已被表征，并可进行靶向治疗，以反映精准医学向前发展的力量。
Primary immunodeficiency disorders (PIDs) represent a range of genetically determined diseases that typically have increased susceptibility to infections and in many also have evidence of immune dysregulation that often presents as autoimmunity. Most recently, the concept of gain of function (GOF) mutations associated with PIDs has become well recognized and adds a new dimension to the understanding of this group of disorders moving beyond the more commonly seen loss of function mutations. The rapidly expanding genetic defects that have been identified in previously uncharacterized PIDs has opened up the potential for targeted therapy directed at the specific disease-causing abnormality. This has been driven by linking PID specific genetic defects to the associated unique abnormalities in cellular signaling pathways amenable to directed therapies. These include agents that either block over active or enhance under responsive cellular pathways. Selected primary immunodeficiences were chosen, whose genetic defects have been recently characterized and are amenable to targeted therapy, as a reflection of the power of precision medicine forward.