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



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.



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.



RA-related autoimmunity is associated with both quantitative and qualitative subclinical ILD phenotypes on CT, particularly among ever smokers.
Department of Medicine, Columbia University Medical Center, New York, New York, USA.
Elana J
EJ
Bernstein
Department of Medicine, Columbia University Medical Center, New York, New York, USA.|Department of Epidemiology, Columbia University Medical Center, New York, New York, USA.
R Graham
RG
Barr
Department of Radiology, Columbia University Medical Center, New York, New York, USA.
John H M
JHM
Austin
Department of Medicine and Center for Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Steven M
SM
Kawut
Department of Medicine, University of Washington, Seattle, Washington, USA.
Ganesh
G
Raghu
Department of Medicine, Columbia University Medical Center, New York, New York, USA.
Jessica L
JL
Sell
Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Eric A
EA
Hoffman
Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
John D
JD
Newell
Department of Radiology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
Jubal R
JR
Watts
Department of Radiology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
P Hrudaya
PH
Nath
Department of Radiology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
Sushil K
SK
Sonavane
Department of Medicine, Columbia University Medical Center, New York, New York, USA.
Joan M
JM
Bathon
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Darcy S
DS
Majka
Department of Medicine, Columbia University Medical Center, New York, New York, USA.|Department of Epidemiology, Columbia University Medical Center, New York, New York, USA.
David J
DJ
Lederer
D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011446:Prospective Studies; D012217:Rheumatoid Factor / Q000097:blood; D012907:Smoking / Q000453:epidemiology / Q000276:immunology; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology
D001323:Autoantibodies; D007075:Immunoglobulin M; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor
Clinical Epidemiology; Connective tissue disease associated lung disease; Interstitial Fibrosis; Rheumatoid lung disease