Alpha-1 antitrypsin deficiency (AATD) is considered one of the most common genetic diseases and is characterised by the misfolding and polymerisation of the alpha-1 antitrypsin (AAT) protein within hepatocytes. The relevance of circulating polymers (CP) of AAT in the pathogenesis of lung and liver disease is not completely understood. Therefore, the main objective of our study was to determine whether there is an association between the levels of CP of AAT and the severity of lung and liver disease. This was a cross-sectional study in patients with different phenotypes of AATD and controls. To quantify CP, a sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT polymers. Sociodemographic data, clinical characteristics, and liver and lung parameters were collected. A cohort of 70 patients was recruited: 32 Pi*ZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP were compared with a control group of 47 individuals (35 Pi*MM and 12 Pi*MS). ZZ patients had the highest concentrations of CP (p < 0.001) followed by Z heterozygous. The control group and patients with Pi*SS and Pi*SI had the lowest CP concentrations. Pi*ZZ also had higher levels of liver stiffness measurements (LSM) than the remaining AATD patients. Among patients with one or two Z alleles, two patients with lung and liver impairment showed the highest concentrations of CP (47.5 µg/mL), followed by those with only liver abnormality (n = 6, CP = 34 µg/mL), only lung (n = 18, CP = 26.5 µg/mL) and no abnormalities (n = 23, CP = 14.3 µg/mL). Differences were highly significant (p = 0.004). Non-augmented Pi*ZZ and Z-patients with impaired lung function and increased liver stiffness presented higher levels of CP than other clinical phenotypes. Therefore, CP may help to identify patients more at risk of developing lung and liver disease and may provide some insight into the mechanisms of disease.

中文翻译：

---

循环 α-1 抗胰蛋白酶聚合物与肺和肝病之间的关联

α-1 抗胰蛋白酶缺乏症 (AATD) 被认为是最常见的遗传疾病之一，其特征是肝细胞内 α-1 抗胰蛋白酶 (AAT) 蛋白的错误折叠和聚合。AAT 循环聚合物 (CP) 在肺和肝病发病机制中的相关性尚未完全清楚。因此，我们研究的主要目的是确定 AAT 的 CP 水平与肺和肝脏疾病的严重程度之间是否存在关联。这是一项针对具有不同 AATD 表型的患者和对照组的横断面研究。为了量化 CP，使用针对 AAT 聚合物的 2C1 单克隆抗体进行了夹心 ELISA。收集了社会人口统计学数据、临床特征和肝肺参数。招募了 70 名患者的队列：32 Pi*ZZ（11 用于增强疗法）；29 Z-杂合子；9 与其他基因型。将 CP 与 47 人（35 Pi*MM 和 12 Pi*MS）的对照组进行比较。ZZ 患者的 CP 浓度最高（p < 0.001），其次是 Z 杂合子。对照组和 Pi*SS 和 Pi*SI 患者的 CP 浓度最低。Pi*ZZ 的肝脏硬度测量 (LSM) 水平也高于其余 AATD 患者。在具有一个或两个 Z 等位基因的患者中，两名肺和肝受损患者的 CP 浓度最高（47.5 µg/mL），其次是仅有肝脏异常的患者（n = 6，CP = 34 µg/mL），仅肺（n = 18，CP = 26.5 µg/mL）且无异常（n = 23，CP = 14.3 µg/mL）。差异非常显着（p = 0.004）。肺功能受损和肝硬度增加的非增强 Pi*ZZ 和 Z 患者的 CP 水平高于其他临床表型。因此，CP 可能有助于识别更易患肺和肝病的患者，并可能提供对疾病机制的一些见解。