Malondialdehyde-Acetaldehyde Adducts and Antibody Responses in Rheumatoid Arthritis-Interstitial Lung Disease

Details

• Alternative Title:
  Arthritis Rheumatol
• Personal Author:
  England, Bryant R. ; Duryee, Michael J. ; Roul, Punyasha ; Mahajan, Tina D. ; Singh, Namrata ; Poole, Jill A. ; Ascherman, Dana P. ; Caplan, Liron ; Demoruelle, M. Kristen ; Deane, Kevin D. ; Klassen, Lynell W. ; Thiele, Geoffrey M. ; Mikuls, Ted R.
• 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.
  
  
• Subjects:
  Acetaldehyde Aged Antibody Formation Arthritis, Rheumatoid Article Autoantibodies Autoantigens Biomarkers Case-Control Studies Female Humans Interstitial Lung Disease Lung Lung Diseases, Interstitial Male Malondialdehyde Middle Aged Pathogenesis Rheumatoid Arthritis

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• Source:
  Arthritis Rheumatol. 71(9):1483-1493
• Pubmed ID:
  30933423
• Pubmed Central ID:
  PMC6717041
• Document Type:
  Journal Article
• 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/ ; University of Nebraska Medical Center Physician-Scientist Training ProgramInternational/
• Volume:
  71
• Issue:
  9
• NIOSHTIC Number:
  nn:20065183
• Collection(s):
  CDC Public Access National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:89f3d52f813c4e7a814364fc8836637033ce2f0579acee02fdbe33d66d1236ed5432250e0e57ae3a75b4eac4d92d89b6dff63c9ada7cbe7f15eac018c32d1271
• Download URL:
  https://stacks.cdc.gov/view/cdc/113139/cdc_113139_DS1.pdf
• File Type:
  [PDF - 986.99 KB ]