Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis

Thorax. 2016 Dec;71(12):1082-1090. doi: 10.1136/thoraxjnl-2016-208932. Epub 2016 Sep 8.

Abstract

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.

Keywords: Clinical Epidemiology; Connective tissue disease associated lung disease; Interstitial Fibrosis; Rheumatoid lung disease.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / blood*
  • Autoimmunity
  • Cross-Sectional Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin M / blood
  • Lung Diseases, Interstitial / complications
  • Lung Diseases, Interstitial / diagnostic imaging
  • Lung Diseases, Interstitial / epidemiology
  • Lung Diseases, Interstitial / immunology*
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology
  • Prospective Studies
  • Rheumatoid Factor / blood
  • Smoking / epidemiology
  • Smoking / immunology
  • Tomography, X-Ray Computed
  • United States / epidemiology

Substances

  • Autoantibodies
  • Immunoglobulin M
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rheumatoid Factor