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Malondialdehyde-Acetaldehyde Adducts and Antibody Responses in Rheumatoid Arthritis-Interstitial Lung Disease
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9 2019
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Source: Arthritis Rheumatol. 71(9):1483-1493
[PDF-986.99 KB]
Details:
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Alternative Title:Arthritis Rheumatol
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Personal Author:
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Description:Objective:
Compare serum anti-malondialdehyde acetaldehyde (MAA) antibodies and MAA expression in lung tissues of patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) with controls.
Methods:
Anti-MAA antibody (IgA, IgM, IgG) concentrations were measured in validated RA-ILD cases and compared to RA patients with chronic obstructive pulmonary disease (COPD) and RA patients without lung disease. Associations of anti-MAA antibody with RA-ILD was assessed using multivariable logistic regression. Lung tissues from patients with RA-ILD, other ILD, emphysema, and controls (n=3/group) were stained for MAA, citrulline, macrophages (CD68), T cells (CD3), B cells (CD19/CD27), and extracellular matrix proteins (type-II collagen, fibronectin, vimentin). Tissue expression and co-localization with MAA was quantified and compared.
Results:
Among 1823 RA patients, 90 had prevalent RA-ILD. Serum IgA and IgM anti-MAA antibody concentrations were higher in RA-ILD than RA+COPD or RA alone (p=0.005). After adjusting for covariates, the highest quartiles of IgA (OR 2.09; 95% CI 1.11-3.90) and IgM (OR 2.23; 95% CI 1.19-4.15) anti-MAA antibody were significantly associated with the presence of RA-ILD. MAA expression was greater in RA-ILD lung tissues than all other groups (p<0.001) and co-localized with citrulline (r=0.79), CD19+ B cells (r=0.78), and extracellular matrix proteins (type-II collagen [r=0.72] and vimentin [r=0.77]) to the greatest degree in RA-ILD.
Conclusion:
Serum IgA and IgM anti-MAA antibody is associated with ILD among RA patients. MAA is highly expressed in lung tissues in RA-ILD where it co-localizes with other RA autoantigens, autoreactive B cells, and extracellular matrix proteins, underscoring its potential role in RA-ILD pathogenesis.
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Subjects:
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Source:
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Pubmed ID:30933423
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Pubmed Central ID:PMC6717041
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Document Type:
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Funding:CX000896/US Department of Veterans AffairsInternational/ ; Internal Medicine Scientist Development Award, and Mentored Scholars ProgramInternational/ ; R01 ES019325/ES/NIEHS NIH HHSUnited States/ ; U54 OH010162/OH/NIOSH CDC HHSUnited States/ ; U54 GM115458/GM/NIGMS NIH HHSUnited States/ ; ... More +
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Volume:71
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Issue:9
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