Chorostowska-Wynimko Joanna, Gawryluk Dariusz, Struniawski Radosław, Popławska Beata, Fijołek Justyna
Laboratory of Molecular Diagnostics and Immunology , National Institute of Tuberculosis and Lung Diseases, Warsaw.
Pneumonol Alergol Pol. 2013;81(4):319-22.
Inherited alpha-1 antitrypsin (AAT) deficiency is one of the three most common genetic disorders in Caucasians. It considerably increases the risk of progressive obstructive lung diseases, mostly chronic obstructive pulmonary disease. It has also been suggested that AAT deficiency might be instrumental vasculitis associated with the anti-neutrophil cytoplasm antibodies (cANCA) and subsequent lung tissue injury.
We present the results from a pilot study involving 51 patients with granulomatosis with polyangiitis, formerly known as Wegener's granulomatosis (GPA), 43 of whom were cANCA positive. The control group consisted of 658 individuals. AAT blood concentration assessment by nephelometry, phenotyping by isoelectrofocusing and real-time PCR genotyping were performed.
Deficiency alleles PIZ and PIS were detected in 3 (5.88%) and in 2 patients (3.92%) with GPA, respectively. All of them were cANCA positive. In the controls, PIZ was observed in 2.8% while PIS in 1.5% of cases. Accordingly, the increased incidence of main deficiency alleles was demonstrated in GPA, and particularly in cANCA+GPA patients, when compared to the controls. The estimated frequency for PIZ in GPA, cANCA+GPA patients and controls was, respectively, 29.4/1000, 34.9/1000 and 13.7/1000, whereas for PIS it was 19.2/1000, 23.2/10,00 and 7.6/1000. However, the observed differences did not reach statistical significance due to the considerable size disproportion between groups. CONSCLUSIONS: We believe that our preliminary data confirm the clinical importance of AAT deficiency in GPA patients and the need to screen for AAT deficiency alleles. The study is on-going.
遗传性α-1抗胰蛋白酶（AAT）缺乏症是白种人中最常见的三种遗传性疾病之一。它显著增加了进行性阻塞性肺部疾病的风险，主要是慢性阻塞性肺疾病。也有人提出，AAT缺乏可能与抗中性粒细胞胞浆抗体（cANCA）相关的血管炎及随后的肺组织损伤有关。
我们展示了一项试点研究的结果，该研究涉及51例肉芽肿性多血管炎患者，以前称为韦格纳肉芽肿（GPA），其中43例cANCA呈阳性。对照组由658名个体组成。通过散射比浊法进行AAT血浓度评估，通过等电聚焦进行表型分析，并进行实时PCR基因分型。
在3例（5.88%）GPA患者和2例（3.92%）患者中分别检测到缺陷等位基因PIZ和PIS。他们均为cANCA阳性。在对照组中，PIZ在2.8%的病例中被观察到，而PIS在1.5%的病例中被观察到。因此，与对照组相比，GPA患者，特别是cANCA+GPA患者中主要缺陷等位基因的发生率有所增加。GPA患者、cANCA+GPA患者和对照组中PIZ的估计频率分别为29.4/1000、34.9/1000和13.7/1000，而PIS的估计频率分别为19.2/1000、23.2/1000和7.6/1000。然而，由于组间规模差异较大，观察到的差异未达到统计学意义。结论：我们认为我们的初步数据证实了AAT缺乏在GPA患者中的临床重要性以及筛查AAT缺乏等位基因的必要性。该研究正在进行中。
