a Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre , Beaumont Hospital , Dublin , Ireland.
Expert Rev Respir Med. 2016 Feb;10(2):207-22. doi: 10.1586/17476348.2016.1127759. Epub 2015 Dec 18.
Alpha-1 antitrypsin (AAT) deficiency (AATD) has traditionally been thought of as a genetic disorder characterized by lung destruction and early emphysema in a low AAT, and high neutrophil elastase (NE) environment in the lungs of affected individuals. Recently, a growing body of evidence has emerged to support the hypothesis that tumor necrosis factor alpha (TNF-α) is essential in the pathogenesis of both genetic AATD and non-genetic chronic obstructive pulmonary disease (COPD). Reports have highlighted the importance of TNF-α driven immune cell dysfunction in the development of lung disease in AATD. The authors discuss the role of AAT as a key modulator of TNF-α signaling firstly in the setting of AATD and secondly in other conditions where AAT augmentation therapy has potential utility as a novel therapy.
α-1 抗胰蛋白酶（AAT）缺乏症（AATD）传统上被认为是一种遗传性疾病，其特征是 AAT 水平低、肺部破坏和早期肺气肿，以及受影响个体肺部的中性粒细胞弹性蛋白酶（NE）水平高。最近，越来越多的证据支持肿瘤坏死因子-α（TNF-α）在遗传性 AATD 和非遗传性慢性阻塞性肺疾病（COPD）发病机制中的重要作用。有报道强调了 TNF-α 驱动的免疫细胞功能障碍在 AATD 中肺病发展中的重要性。作者首先讨论了 AAT 作为 TNF-α 信号关键调节剂的作用，一是在 AATD 中，二是在其他情况下，AAT 增强治疗作为一种新的治疗方法具有潜在的应用价值。
