Identification of alpha-enolase as an autoantigen associated with severe asthma.

BACKGROUND

Approximately 5% to 10% of patients with asthma have severe disease that is not effectively controlled by typical therapies. The existence of an autoantigen associated with severe asthma has been previously reported.

OBJECTIVE

We attempted to identify the autoantigen.

METHODS

Severe asthma was defined as patients having at least 1 severe asthmatic exacerbation requiring an emergency department visit or admission in the last year despite continuous typical therapies. Autoantibodies to airway epithelial cells (A549) were examined in sera from patients with severe asthma by immunoblot analysis.

RESULTS

IgG autoantibodies to the 52-kd airway epithelial cell antigen were detected in sera from 32 of 78 patients with severe asthma (41%), 9 of 83 patients with mild-to-moderate asthma (11%), and 2 of 58 healthy controls (3%; P < .001). The 52-kd autoantigen was identified as alpha-enolase by mass spectrometry analysis and confirmed by using recombinant human alpha-enolase protein. The detection of IgG autoantibodies to alpha-enolase was the most significant indicator for distinguishing severe asthma from mild-to-moderate asthma, even after adjusting for the effects of other clinical variables, including age, sex, atopy, and FEV(1) (adjusted odds ratio, 5.2; 95% CI, 2.1-12.9; P < .001).

CONCLUSION

The alpha-enolase was identified as an autoantigen associated with severe asthma. Further studies are needed to determine the significance of this autoantigen in severe asthma.

CLINICAL IMPLICATIONS

IgG autoantibodies to alpha-enolase could be a biological marker for severe asthma.