Pneumology Department, Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, P. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.
Respir Res. 2021 Sep 15;22(1):244. doi: 10.1186/s12931-021-01842-5.
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 PiZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP were compared with a control group of 47 individuals (35 PiMM and 12 PiMS). ZZ patients had the highest concentrations of CP (p < 0.001) followed by Z heterozygous. The control group and patients with PiSS and PiSI had the lowest CP concentrations. PiZZ 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.
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，其特征是肝细胞内的 α-1 抗胰蛋白酶（AAT）蛋白错误折叠和聚合。循环中的 AAT 聚合物（CP）在肺病和肝病发病机制中的相关性尚不完全清楚。因此，我们研究的主要目的是确定 AAT 的 CP 水平与肺病和肝病的严重程度之间是否存在关联。
这是一项在具有不同 AATD 表型的患者和对照组中进行的横断面研究。为了定量 CP，使用针对 AAT 聚合物的 2C1 单克隆抗体进行夹心 ELISA。收集社会人口统计学数据、临床特征以及肝和肺参数。
共招募了 70 名患者：32 名 PiZZ（11 名接受增敏治疗）；29 名 Z 杂合子；9 名其他基因型。将 CP 与 47 名对照组个体（35 名 PiMM 和 12 名 PiMS）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 PiSS 和 PiSI 患者的 CP 浓度最低。PiZZ 患者的肝硬度测量值（LSM）也高于其他 AATD 患者。在携带一个或两个 Z 等位基因的患者中，两名肺和肝损伤患者的 CP 浓度最高（47.5μg/mL），其次是仅存在肝异常的患者（n=6，CP=34μg/mL），仅存在肺异常的患者（n=18，CP=26.5μg/mL）和无异常的患者（n=23，CP=14.3μg/mL）。差异具有高度显著性（p=0.004）。
未接受增敏治疗的 Pi*ZZ 和 Z 患者，肺功能受损和肝硬度增加，CP 水平高于其他临床表型。因此，CP 可能有助于识别更易发生肺病和肝病的患者，并为疾病机制提供一些见解。
