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

Details

• Journal Article:
  Arthritis and Rheumatology
• Personal Author:
  Ascherman, Dana P. ; Caplan, Liron ; Deane, Kevin D. ; Demoruelle, M. Kristen ; Duryee, Michael J. ; England, Bryant R. ; Klassen, Lynell W. ; Mahajan, Tina D. ; Mikuls, Ted R. ; Poole, Jill A. ; Roul, Punyasha ; Singh, Namrata ; Thiele, Geoffrey M.
• Description:
  Objective: To compare serum anti-malondialdehyde-acetaldehyde (anti-MAA) antibody levels and MAA expression in lung tissue from patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) to those found in controls. Methods: Anti-MAA antibody (IgA, IgM, IgG) concentrations were measured in patients with RA-ILD and compared to those of RA patients with chronic obstructive pulmonary disease (COPD) and RA patients without lung disease. Associations between anti-MAA antibody with RA-ILD were assessed using multivariable logistic regression. Lung tissue from patients with RA-ILD, other ILD, or emphysema, and from controls (n = 3 per 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 colocalization with MAA were quantified and compared. Results: Among 1,823 RA patients, 90 had prevalent RA-ILD. Serum IgA and IgM anti-MAA antibody concentrations were higher in RA-ILD than in RA with COPD or RA alone (P = 0.005). After adjustment for covariates, the highest quartiles of IgA anti-MAA antibody concentration (odds ratio 2.09 [95% confidence interval 1.11-3.90]) and IgM (odds ratio 2.23 [95% confidence interval 1.19-4.15]) were significantly associated with the presence of RA-ILD. MAA expression in RA-ILD lung tissue was greater than in tissue from all other groups (P < 0.001), and it colocalized 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 RA-ILD lung tissue, where it colocalizes with other RA autoantigens, autoreactive B cells, and extracellular matrix proteins, highlighting its potential role in the pathogenesis of RA-ILD. [Description provided by NIOSH]
• Subjects:
  Acetaldehyde Antibodies Antibody Formation Arthritis, Rheumatoid Autoantibodies Autoantigens Case-Control Studies Immune System Lung Lung Diseases Malondialdehyde Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Rheumatoid disorders; Autoimmune diseases; Respiratory diseases; Immune reaction; Antibody response; Antibodies
• Source:
  Arthritis Rheumatol 2019 Sep; 71(9):1483-1493
• ISSN:
  2326-5191
• Pubmed ID:
  30933423
• Pubmed Central ID:
  PMC6717041
• Document Type:
  Text
• 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/
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; Florida ; Iowa ; Nebraska ; OSHA Region 4 ; OSHA Region 7 ; OSHA Region 8
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  19 pdf pages
• Volume:
  71
• Issue:
  9
• NIOSHTIC Number:
  nn:20065183
• Contact Point Address:
  Bryant R. England, MD, 986270 Nebraska Medical Center, Omaha, NE 68198-6270
• Email:
  bryant.england@unmc.edu
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• 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 ]