S15 Proteinase 3 activity in PiSZ alpha-1 antitrypsin deficiency and non-deficient chronic obstructive pulmonary disease
2018
Introduction Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible inflammatory disease caused by excess neutrophilic inflammation resulting in an enhanced inflammatory response in the airways. It is widely accepted that the inflammation and tissue damage relates to a proteinase/anti-proteinase imbalance with both neutrophil elastase (NE) and proteinase 3 (PR3) implicated.1 2 PR3 may be more important especially in alpha-1 antitrypsin (AAT) deficiency (AATD), where mutations in SERPINA1 results in little/no production of the anti-proteinase AAT preventing effective inhibition of both NE and especially PR3.3 The relationship of the SZ form of AAT to increase susceptibility to develop COPD remains uncertain. We hypothesised that patients with non-deficient COPD would have increased PR3 activity compared to healthy smokers, but similar to patients with the intermediate PiSZ AATD indicating no increased susceptibility. Methods PR3 activity was measured using a novel indirect ELISA based on a specific fibrinogen cleavage product (Aα–Val541). Plasma samples from patients with non-deficient COPD (n=31) and PiSZ AATD (n=95) were tested alongside healthy smoking controls (n=52) for the presence of this marker. Results Patients with usual COPD had an average FEV1/FCV ratio of 0.47 (SD ±0.17), compared to 0.63 (±0.21) in PiSZ AATD patients, and 0.77 (±0.07) in healthy patients. The Aα-Val541 concentration was increased (p 0.99). Conclusions These findings build a proteolytic enzyme activity profile in COPD patients, supporting the role of the proteinase/anti-proteinase imbalance in the pathophysiology of COPD. The data does not provide evidence to support an increased role in patients with PiSZ AATD. References Sinden NJ, et al. ERJ2013. Sinden NJ, et al. Am J Physiol Lung Cell Mol Physiol2015. Zorzetto M, et al. Clin Chem2008.
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