Date of Award
MD (Medical Doctor)
Dr Catherine Greene
Professor Noel G. McElvaney
Pulmonary Disease, Chronic Obstructive, Autoimmunity
Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible airflow limitation that is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases (1). There is increasing evidence suggesting that COPD is likely to have an autoimmune component (2-4). Smoking causes an imbalance of protease and anti-protease activity in the lung and elastin peptides or collagen breakdown products (proline-glycine-proline/PGF') can be generated as a result. These peptides can act as neoantigens and induce an autoimmune response. Similar to COPD, Z alpha-1 antitrypsin deficiency (Z-AlATD) and cystic fibrosis (CF) are associated with impaired pulmonary anti-protease defences leading to unopposed protease activity which can potentially generate neoantigens from lungderived elastin or collagen. In this study we show that anti-elastin and anti-PGP autoantibodies are not significantly different in patients with COPD, Z-AlATD and CF when compared to healthy controls. As these effects could be tissue specific and local intrapulmonary autoimmunity may contribute to disease pathogenesis in chronic inflammatory lung disease, bronchoalveolar lavage fluid (BALF) anti-elastin antibodies are investigated. Here we show that BALF anti-elastin autoantibodies are present in COPD and Z-A1ATD but not in CF and these antibodies can cause T cell proliferation. The lack of anti-elastin antibodies in CF is due to neutrophil elastase (NE) degradation.
Autoantibodies against neutrophil granule proteins such as proteinase 3 (PR3) and neutrophil elastase (NE) have been linked with patients with Z-AlATD. Here we show that antibodies against primary neutrophil granule proteins (PR3 and NE) as well as secondary neutrophil granule proteins (lactoferrin) are present in plasma of patients with Z-A1 ATD.
In conclusion, this study highlights that anti-elastin antibodies are tissue specific and are detected in the BALF of COPD and Z-AlATD despite the absence of these autoantibodies in the plasma. The low level of BALF anti-elastin antibodies in CF may have a protective role. It also highlights the potential role of therapeutic agents targeting these autoantibodies in the lungs. Lastly, neutrophil granule proteins are important antimicrobials and autoantibodies against primary (PR3 and NE) as well as secondary neutmphil granule proteins (lactoferrin) are detected in patients with ZAlATD in this study. Similarly, there may be a potential role of therapeutic agents targeting these autoantibodies.
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Low TB. Autoimmunity in Chronic Inflammatory Lung Disease [MD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2010.