Dual autoantibody seropositivity may increase risk for prevalent rheumatoid arthritis-ILD

Combined rheumatoid factor and anti-citrullinated protein antibody seropositivity was strongly associated with prevalent rheumatoid arthritis-associated interstitial lung disease in a cohort of U.S. veterans, researchers reported.

The researchers did not find an association between dual autoantibody positivity and incident rheumatoid arthritis-associated ILD.

Moreover, those with higher individual autoantibody concentrations appear to have an increased risk for incident rheumatoid arthritis-associated ILD, according to the data published in the Annals of the American Thoracic Society.

“An improved understanding of the relationship between these autoantibodies and [rheumatoid arthritis]-ILD could inform important underlying disease mechanisms and potentially strengthen their clinical utility,” Jake G. Natalini, MD, internist in the division of pulmonary, allergy and critical care and the Center for Clinical Epidemiology and Biostatistics at Perelman School of Medicine at the University of Pennsylvania, and colleagues wrote.
The researchers used the Veterans Affairs Rheumatoid Arthritis prospective registry to perform a cross-sectional study and a retrospective cohort study of incident ILD diagnosed after at least 1 year of longitudinal follow-up. The cohort included 2,328 participants (median age, 64 years; 89.3% men).

More than 4% of participants had prevalent ILD at the time of enrollment. Among those without prevalent ILD at enrollment, 3.7% received a subsequent diagnosis of incident ILD (5.8 cases per 1,000 person-years) during 14,281 patient-years of follow-up.

The probability of prevalent ILD was higher among participants with combined rheumatoid factor and anti-citrullinated protein antibody seropositivity compared with participants who were seronegative (OR = 2.9; 95% CI, 1.24-6.78), according to the results.

The researchers reported a monotonic association between prevalent ILD and low-positive (15-45 IU/mL) rheumatoid factor titers (OR = 2.69; 95% CI, 1.11-6.51) and high-positive (> 45 IU/mL) rheumatoid factor titers (OR = 3.4; 95% CI, 1.61-7.18). Participants with high-positive anti-citrullinated protein antibody titers had an increased risk for prevalent ILD compared with participants who were negative (OR = 1.91; 95% CI, 1.04-3.49), according to the results.

Rheumatoid factor titers greater than 90 IU/mL were independently correlated with an increased risk for incident ILD (HR = 1.68; 95% CI, 1.02-2.77).

The researchers did not observe an association between combined rheumatoid factor and anti-citrullinated protein antibody seropositivity or their respective titers and increased risk for incident ILD.

“Our investigation of combined autoantibody status and individual autoantibody concentrations advances our understanding of the role of autoantibodies in rheumatoid arthritis-ILD pathogenesis and demonstrates the need for the development and validation of rheumatoid arthritis-ILD risk models to enhance its identification,” the researchers wrote.