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

Details

• Alternative Title:
  Arthritis Rheumatol
• Personal Author:
  Aripova, Nozima ; Thiele, Geoffrey M. ; Duryee, Michael J. ; Hunter, Carlos D. ; Yang, Yangyuna ; Roul, Punyasha ; Ascherman, Dana P. ; Matson, Scott M. ; Kunkel, Gary ; Cannon, Grant W. ; Wysham, Katherine D. ; Kerr, Gail S. ; Monach, Paul A. ; Baker, Joshua F. ; Poole, Jill A. ; Mikuls, Ted R. ; England, Bryant R.
• Description:
  Objective:
  
  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 U.S. 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 ELISA. 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 RA participants (88% male, mean age 64 years), there were 114 prevalent and 136 incident RA-ILD cases (average time to diagnosis: 6.6 years). Higher IgM anti-MAA-collagen (per 1 SD: aOR 1.28 [1.02–1.61]), IgA anti-MAA-fibrinogen (aOR 1.48 [1.14–1.92]), and IgA (aOR 1.78 [1.34–2.37]) and IgG (aOR 1.48 [1.14–1.92]) anti-MAA-vimentin antibodies were associated with prevalent RA-ILD. In incident analyses, higher IgA (per 1 SD: aHR 1.40 [1.11–1.76]) and IgM (aHR 1.29 [1.04–1.60]) anti-MAA-albumin antibody concentrations were associated with increased ILD risk. Participants with IgA (aHR 2.13 [1.16–3.90]) or IgM (aHR 1.98 [1.08–3.64]) anti-MAA-albumin antibody concentrations in the highest quartile had an approximate 2-fold increased risk of incident RA-ILD. Across all isotypes, anti-MAA-fibrinogen, -collagen, and -vimentin antibodies were not significantly associated with incident RA-ILD.
  
  Conclusions:
  
  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.
  
  
• Subjects:
  Acetaldehyde Aged Arthritis, Rheumatoid Autoantibodies Collagen Female Fibrinogen Humans Immunoglobulin A Immunoglobulin G Immunoglobulin M Incidence Lung Diseases, Interstitial Male Middle Aged Prevalence Prospective Studies Serum Albumin United States Veterans Vimentin

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• Keywords:
  Autoantibodies Biomarkers Interstitial Lung Disease Post-translational Modifications Rheumatoid Arthritis
• Source:
  Arthritis Rheumatol. 76(9):1353-1363
• Pubmed ID:
  38766737
• Pubmed Central ID:
  PMC11349468
• Document Type:
  Journal Article
• Funding:
  PR200793/U.S. Department of Defense/ ; P20GM130423/GM/NIGMS NIH HHSUnited States/ ; BX004600/Veterans Affairs Biomedical Laboratory Research and Development/ ; IK CX002351/Veterans Affairs Clinical Science Research and Development/ ; I01 RX003644/RX/RRD VAUnited States/ ; P20 GM130423/GM/NIGMS NIH HHSUnited States/ ; I01 BX003635/BX/BLRD VAUnited States/ ; IK2 CX002351/CX/CSRD VAUnited States/ ; U54 GM115458/GM/NIGMS NIH HHSUnited States/ ; Rheumatology Research Foundation/ ; I01 BX004660/BX/BLRD VAUnited States/ ; IK2 CX002203/CX/CSRD VAUnited States/ ; R01 OH012045/OH/NIOSH CDC HHSUnited States/ ; U54GM115458/GM/NIGMS NIH HHSUnited States/ ; I01 CX001703/CX/CSRD VAUnited States/
• Volume:
  76
• Issue:
  9
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:26c59db16b3f7f59422d4f44634c1f707bc37833cf73f1949badd74bb782b9f35f81cd02fa0cde080a6b7608e0ba836bbbf67f3a2744c7e29b9f07fd10a0abf5
• Download URL:
  https://stacks.cdc.gov/view/cdc/160663/cdc_160663_DS1.pdf
• File Type:
  [PDF - 649.85 KB ]