Antibodies to Malondialdehyde-Acetaldehyde Adduct Are Associated with Prevalent and Incident Rheumatoid Arthritis-Associated Interstitial Lung Disease in US Veterans

Details

• Personal Author:
  Aripova N ; Ascherman DP ; Baker JF ; Cannon GW ; Duryee MJ ; England BR ; Hunter CD ; Kerr GS ; Kunkel G ; Matson SM ; Mikuls TR ; Monach PA ; Poole JA ; Roul P ; Thiele GM ; Wysham KD ; Yang Y
• Description:
  Objective: The objective of this study is to determine the associations of protein-specific anti-malondialdehyde-acetaldehyde (MAA) antibodies with prevalent and incident rheumatoid arthritis-interstitial lung disease (RA-ILD). Methods: Within a multicenter, prospective cohort of US veterans with RA, RA-ILD was validated by medical record review of clinical diagnoses, chest imaging, and pathology. Serum antibodies to MAA-albumin, MAA-collagen, MAA-fibrinogen, and MAA-vimentin (IgA, IgM, and IgG) were measured by a standardized enzyme-linked immunosorbent assay. Associations of anti-MAA antibodies with prevalent and incident RA-ILD were assessed using multivariable regression models adjusting for established RA-ILD risk factors. Results: Among 2,739 participants with RA (88% male, mean age of 64 years), there were 114 with prevalent and 136 with incident RA-ILD (average time to diagnosis: 6.6 years). Higher IgM anti-MAA-collagen (per 1 SD: adjusted odds ratio [aOR] 1.28, 95% confidence interval [CI] 1.02-1.61), IgA anti-MAA-fibrinogen (aOR 1.48, 95% CI 1.14-1.92), and IgA (aOR 1.78, 95% CI 1.34-2.37) and IgG (aOR 1.48, 95% CI 1.14-1.92) anti-MAA-vimentin antibodies were associated with prevalent RA-ILD. In incident analyses, higher IgA (per one SD: adjusted hazards ratio [aHR] 1.40, 95% CI 1.11-1.76) and IgM (aHR 1.29, 95% CI 1.04-1.60) anti-MAA-albumin antibody concentrations were associated with increased ILD risk. Participants with IgA (aHR 2.13, 95% CI 1.16-3.90) or IgM (aHR 1.98, 95% CI 1.08-3.64) anti-MAA-albumin antibody concentrations in the highest quartile had an approximately two-fold increased risk of incident RA-ILD. Across all isotypes, anti-MAA-fibrinogen, anti-MAA-collagen, and anti-MAA-vimentin antibodies were not significantly associated with incident RA-ILD. Conclusion: Protein-specific anti-MAA antibodies to collagen, fibrinogen, and vimentin were associated with prevalent RA-ILD. IgA and IgM anti-MAA-albumin antibodies were associated with a higher risk of incident RA-ILD. These findings suggest that MAA modifications and resultant immune responses may contribute to RA-ILD pathogenesis. [Description provided by NIOSH]
• Subjects:
  Antibodies Immune System Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Antibody Response Autoimmune Diseases Immune Reaction Military Personnel Respiratory Diseases Rheumatoid Disorders
• ISSN:
  2326-5191
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  District of Columbia ; Kansas ; Massachusetts ; Nebraska ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 7 ; OSHA Region 8 ; Pennsylvania ; Utah
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  76
• Issue:
  9
• NIOSHTIC Number:
  nn:20070121
• Citation:
  Arthritis Rheumatol 2024 Sep; 76(9):1353-1363
• Email:
  bryant.england@unmc.edu
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center
• Peer Reviewed:
  True
• Start Date:
  20210901
• Source Full Name:
  Arthritis and Rheumatology
• End Date:
  20250831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:497993c500b29dbfef0320c6c5d4c507ee66830f04e386013e138deb8246e33a4c6758ecc0b156b80162548ec0aa171202347f4fdf223f94e3b3b295458a6a68
• Download URL:
  https://stacks.cdc.gov/view/cdc/208406/cdc_208406_DS1.pdf
• File Type:
  [PDF - 613.22 KB ]