Association of alpha(1)-antichymotrypsin deficiency with milder lung disease in patients with cystic fibrosis.

Abstract

BACKGROUND:

Cystic fibrosis (CF) is characterised by an excess of free proteinases that destroy lung tissue. Despite this, previous studies have shown that patients with CF with a mild deficiency variant of the proteinase inhibitor alpha(1)-antitrypsin have less, rather than more, severe pulmonary disease. Alpha(1)-antichymotrypsin is another important serine proteinase inhibitor that protects the lung against proteolytic attack, and point mutations in the alpha(1)-antichymotrypsin gene that result in plasma deficiency are associated with chronic obstructive pulmonary disease.

METHODS:

The effect of alpha(1)-antichymotrypsin deficiency and the -15 alpha(1)-antichymotrypsin signal peptide genotype on lung function was assessed in patients with CF.

RESULTS:

One hundred and fifty seven patients with CF were screened and 10 were identified with a plasma deficiency of alpha(1)-antichymotrypsin (plasma concentration <0.2 g/l). In a multivariate analysis these individuals had significantly less severe lung disease than those who had normal or raised levels of alpha(1)-antichymotrypsin: forced expiratory volume in one second (FEV(1)) 69.9% predicted versus 53. 2% predicted (p=0.04) and chest radiographic score of 7.2 versus 9.7 (p=0.03) for those with and without alpha(1)-antichymotrypsin deficiency, respectively. The -15 signal peptide genotype did not affect plasma levels, but the -15 Ala/Ala signal peptide genotype was over-represented in individuals with CF compared with healthy blood donor controls.

CONCLUSION:

These data indicate that deficiency of alpha(1)-antichymotrypsin is associated with less severe pulmonary disease in patients with CF, and support our previous observations that mild genetic deficiency of a proteinase inhibitor is associated with an improved outcome.

• Authors: R Mahadeva, L Sharples, R I Ross-Russell, A K Webb, D Bilton, D A Lomas
• Journal: Thorax (Thorax) Vol. 56 Issue 1 Pg. 53-8 (Jan 2001) ISSN: 0040-6376 [Print] England
• PMID: 11120905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Sorting Signals
• alpha 1-Antichymotrypsin

Topics

• Adult
• Cystic Fibrosis (enzymology, physiopathology)
• Female
• Forced Expiratory Volume (physiology)
• Genotype
• Humans
• Lung Diseases (complications, physiopathology)
• Male
• Multivariate Analysis
• Protein Sorting Signals (genetics, physiology)
• alpha 1-Antichymotrypsin (blood, deficiency, genetics)