Background/Purpose: Approximately 30% of adults diagnosed with interstitial lung disease (ILD) have an underlying established autoimmune disease. Based on the strong links between autoimmunity and ILD, we performed the current study to determine whether serum rheumatoid factor (RF) IgM and IgA and anti-cyclic citrullinated peptide antibody (anti-CCP) were associated with subclinical ILD in a population-based cohort. 

Methods: MESA is a multi-center, prospective cohort study of 6814 men and women aged 45-84 when recruited in 2000-2002 (exam 1) from 6 US sites. RF and anti-CCP were measured via ELISA at exam 1. Cardiac CT scans were performed at exam 1. Participants returned for 4 subsequent exams, the most recent in 2010-2012. High attenuation areas (HAAs) were assessed on exam 1 cardiac CTs and defined as the volume of lung with a CT attenuation value between -600 and -250 Hounsfield units. 2430 full lung CT scans performed from 2010-2012 were each visually inspected by 1 expert radiologist for the presence or absence of ILD and the following interstitial lung abnormalities (ILAs) affecting >5% of any lung zone in a non-dependent fashion: ground glass abnormalities, reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis. RF IgM and IgA and anti-CCP were modeled as the independent continuous variables of interest in linear or Poisson regression models, with HAA and ILA as the dependent variables, adjusting for demographics, anthropometrics, site, smoking, and CT parameters.

Results: RF was measured and HAA quantified in 6736 participants at exam 1; anti-CCP was measured in 6728. Median age was 62 (IQR 53-70). 53% were female, 39% white, 27% African American, 12% Chinese American, and 22% Hispanic. 14% were current smokers; 45% were never smokers. In fully adjusted models, HAA increased by 0.49% per doubling of RF IgM (95% CI 0.11 to 0.86%, p-value = 0.01) and by 0.94% per doubling of RF IgA (95% CI 0.49 to 1.39%, p-value < 0.001). In fully adjusted models, the prevalence of ILA increased by 10% per log unit change in RF IgM (PR 1.10, 95% CI 0.997 to 1.22, p-value = 0.057) and by 17% per log unit change in RF IgA (PR 1.17, 95% CI 1.04 to 1.30, p-value = 0.006). There was no significant association between anti-CCP and HAA or ILA. Among ever smokers, in fully adjusted models, the prevalence of ILA increased by 21% per each natural log unit increase of RF IgM (PR 1.21, 95% CI 1.07 to 1.36), by 21% per each natural log unit increase of RF IgA (PR 1.21, 95% CI 1.08 to 1.36), and by 19% per each log unit increase of anti-CCP (PR 1.19, 95% CI 1.03 to 1.37). Among never smokers, there was no statistically significant association between RF IgM, RF IgA, or anti-CCP and the prevalence of ILA.

Conclusion: In this large population-based multi-ethnic study, we found significant associations between serum levels of RF IgM and RF IgA and subclinical ILD. Moreover, smoking modified the associations of RF and anti-CCP with subclinical ILD. Our findings suggest that RA-related autoimmunity may contribute to the development of ILD in a community-based population sample.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-rheumatoid-factor-and-anti-cyclic-citrullinated-peptide-antibody-are-associated-with-subclinical-interstitial-lung-disease-in-the-multi-ethnic-study-of-atherosclerosis-a-population-based-study/