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Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis
  1. Elana J Bernstein1,
  2. R Graham Barr1,2,
  3. John H M Austin3,
  4. Steven M Kawut4,
  5. Ganesh Raghu5,
  6. Jessica L Sell1,
  7. Eric A Hoffman6,
  8. John D Newell Jr6,
  9. Jubal R Watts Jr7,
  10. P Hrudaya Nath7,
  11. Sushil K Sonavane7,
  12. Joan M Bathon1,
  13. Darcy S Majka8,
  14. David J Lederer1,2
  1. 1Department of Medicine, Columbia University Medical Center, New York, New York, USA
  2. 2Department of Epidemiology, Columbia University Medical Center, New York, New York, USA
  3. 3Department of Radiology, Columbia University Medical Center, New York, New York, USA
  4. 4Department of Medicine and Center for Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
  5. 5Department of Medicine, University of Washington, Seattle, Washington, USA
  6. 6Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
  7. 7Department of Radiology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA
  8. 8Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  1. Correspondence to Dr David J Lederer, Departments of Medicine and Epidemiology (in Pediatrics), Columbia University Medical Center, 161 Fort Washington Ave, Room 3-321A, New York, NY 10032, USA; davidlederer{at}


Background Adults with interstitial lung disease (ILD) often have serologic evidence of autoimmunity of uncertain significance without overt autoimmune disease. We examined associations of rheumatoid arthritis (RA)-associated antibodies with subclinical ILD in community-dwelling adults.

Methods We measured serum rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) and high attenuation areas (HAAs; CT attenuation values between −600 and −250 Hounsfield units) on cardiac CT in 6736 community-dwelling US adults enrolled in the Multi-Ethnic Study of Atherosclerosis. We measured interstitial lung abnormalities (ILAs) in 2907 full-lung CTs at 9.5-year median follow-up. We used generalised linear and additive models to examine associations between autoantibodies and both HAA and ILA, and tested for effect modification by smoking.

Results In adjusted models, HAA increased by 0.49% (95% CI 0.11% to 0.86%) per doubling of RF IgM and by 0.95% (95% CI 0.50% to 1.40%) per RF IgA doubling. ILA prevalence increased by 11% (95% CI 3% to 20%) per RF IgA doubling. Smoking modified the associations of both RF IgM and anti-CCP with both HAA and ILA (interaction p values varied from 0.01 to 0.09). Among ever smokers, HAA increased by 0.81% (95% CI 0.33% to 1.30%) and ILA prevalence increased by 14% (95% CI 5% to 24%,) per RF IgM doubling; and HAA increased by 1.31% (95% CI 0.45% to 2.18%) and ILA prevalence increased by 13% (95% CI 2% to 24%) per anti-CCP doubling. Among never smokers, no meaningful associations were detected.

Conclusions RA-related autoimmunity is associated with both quantitative and qualitative subclinical ILD phenotypes on CT, particularly among ever smokers.

  • Connective tissue disease associated lung disease
  • Rheumatoid lung disease
  • Interstitial Fibrosis
  • Clinical Epidemiology

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