Relative α₁-anti-trypsin deficiency in systemic sclerosis.

Abstract

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.

• Authors: Theresa C Barnes, Andy Cross, Marina E Anderson, Steven W Edwards, Robert J Moots
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 50 Issue 8 Pg. 1373-8 (Aug 2011) ISSN: 1462-0332 [Electronic] England
• PMID: 21454304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• alpha 1-Antitrypsin
• Leukocyte Elastase

Topics

• Cells, Cultured
• Humans
• Leukocyte Elastase (blood)
• Neutrophils (enzymology)
• Scleroderma, Systemic (blood, complications)
• alpha 1-Antitrypsin (blood)
• alpha 1-Antitrypsin Deficiency (blood, complications)