한빛사논문
Quoc Quang Luu,1,2 Tra Cao Thi Bich,1,2 Yoo-Seob Shin,1,2 Eun-Mi Yang,1 Ji-Young Moon,1 and Hae-Sim Park,1,2,*
1Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon
2Department of Biomedical Sciences, Ajou University School of Medicine, Suwon
*Corresponding author
Abstract
Background and objective: Autoimmune mechanisms are involved in airway inflammatory mechanisms of asthma, where antinuclear antibody (ANA) is one of detectable autoantibodies.
To investigate autoimmune mechanisms in severe asthma (SA), we measured ANA levels in association with inflammatory parameters in sputa of the SA group compared to the nonsevere asthma (NSA) group.
Methods: 46 adult asthmatics (17 SA and 29 NSA groups) were enrolled. Lung functions (FEV1%, FEV1/FVC, MMEF%), blood/sputum inflammatory cells were compared. Sputum levels of myeloperoxidase (MPO), eosinophil-derived neurotoxin (EDN), matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and ANA were measured by ELISA.
Results: The SA group had significantly higher ANA levels as well as MMP-9/TIMP-1 levels in sputum than the non-SA group, while FEV1 (%), FVC (%), FEV1/FVC, and MMEF (%) were significantly lower in the SA group than in the non-SA group (P < .050 for all). The cutoff value of sputum ANA level predicting the SA group is 111.8 U/mL with a statistical significance (P = .002, 70.6% sensitivity, 72.4% specificity). Significantly positive correlations were noted between sputum MPO and MMP-9/TIMP-1 levels (r = 0.815, P < .001; r = 0.770, P < .001); significantly negative correlations were found between FEV1 (%) and sputum MMP-9 /TIMP-1 levels (r = -0.341, P < .025; r = -0.489, P < .001)
Conclusion: Neutrophil/NET-induced inflammation is associated with ANA-associated autoimmune response in the asthmatic airway, contributing to asthma severity and lung function declines, in which MMP-9/TIMP-1 are involved. Further studies are needed to evaluate whether epithelial biologics (anti TSLP or IL-33 antibodies) could overcome this autoimmune cascade.
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