Low Teck Boon, Greene Catherine M, O'Neill Shane J, McElvaney Noel G
Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
Pulm Med. 2011;2011:826160. doi: 10.1155/2011/826160. Epub 2011 Mar 31.
Chronic obstructive pulmonary disease (COPD) may be an autoimmune disease. Smoking causes an imbalance of proteases and antiproteases in the lung resulting in the generation of elastin peptides that can potentially act as autoantigens. Similar to COPD, Z alpha-1 antitrypsin deficiency (Z-A1ATD) and cystic fibrosis (CF) are associated with impaired pulmonary antiprotease defences leading to unopposed protease activity. Here, we show that there is a trend towards higher bronchoalveolar lavage fluid (BALF) antielastin antibody levels in COPD and Z-A1ATD and significantly lower levels in CF compared to control BALF; the lower levels in CF are due to the degradation of these antibodies by neutrophil elastase. We also provide evidence that these autoantibodies have the potential to induce T cell proliferation in the emphysematous lung. This study highlights that antielastin antibodies are tissue specific, can be detected at elevated levels in COPD and Z-A1ATD BALF despite their being no differences in their levels in plasma compared to controls, and suggests a therapeutic role for agents targeting these autoantibodies in the lungs.
慢性阻塞性肺疾病（COPD）可能是一种自身免疫性疾病。吸烟会导致肺部蛋白酶和抗蛋白酶失衡，从而产生可能作为自身抗原的弹性蛋白肽。与COPD类似，Zα-1抗胰蛋白酶缺乏症（Z-A1ATD）和囊性纤维化（CF）与肺部抗蛋白酶防御功能受损有关，导致蛋白酶活性不受抑制。在此，我们表明，与对照支气管肺泡灌洗液（BALF）相比，COPD和Z-A1ATD患者的BALF抗弹性蛋白抗体水平有升高趋势，而CF患者的水平则显著降低；CF患者抗体水平较低是由于中性粒细胞弹性蛋白酶对这些抗体的降解所致。我们还提供证据表明，这些自身抗体有可能在肺气肿肺中诱导T细胞增殖。这项研究强调，抗弹性蛋白抗体具有组织特异性，尽管与对照组相比其血浆水平无差异，但在COPD和Z-A1ATD的BALF中可检测到其水平升高，并提示针对这些肺部自身抗体的药物具有治疗作用。
