Relative α1-anti-trypsin deficiency in systemic sclerosis

• Published in: Rheumatology (Oxford, England) England), 2011-08, Vol.50 (8), p.1373-1378
• Main Authors: Barnes, Theresa C., Cross, Andy, Anderson, Marina E., Edwards, Steven W., Moots, Robert J.
• Format: Article
• Language: English
• Subjects: alpha 1-Antitrypsin - blood; alpha 1-Antitrypsin Deficiency - blood; alpha 1-Antitrypsin Deficiency - complications; Basic Science; Cells, Cultured; Humans; Leukocyte Elastase - blood; Neutrophils - enzymology; Scleroderma, Systemic - blood; Scleroderma, Systemic - complications
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/ker123

Objective. Neutrophil elastase is secreted by neutrophils during activation and circulates in the plasma where it can play a role in inflammation and fibrosis. This study examines the role of neutrophil elastase in SSc, a systemic CTD that is typified by vascular dysfunction, tissue fibrosis and inflammation. Methods. Serum neutrophil elastase and α1-anti-trypsin concentrations were assessed in SSc patients and healthy controls by ELISA. Serum neutrophil elastase activity was assessed by the elastase-dependent conversion of methoxy-succinyl-alanyl-alanyl-prolyl-valyl-p-nitroanilide to p-nitroanilide using a colourimetric assay. Elastase concentration and activity were correlated with clinical disease features. Results. Serum neutrophil elastase concentration and activity were equivalent in patients and controls; however, in SSc serum, there was an increase in elastase activity for each unit of elastase concentration (P = 0.03). This was due to a decrease in serum α1-anti-trypsin concentrations (P = 0.04). Serum elastase concentration (P = 0.03) and activity (P = 0.02) were significantly lower in RNP-positive patients and serum elastase concentrations were lower in ANA-positive patients (P = 0.003). Conclusions. Relative deficiency in serum α1-anti-trypsin concentrations in SSc could have important and pathogenically relevant effects since elastase has pro-inflammatory and pro-fibrotic roles. Elastase inhibitors are available in clinical practice and could represent potential therapeutic options in SSc.