Autoantibody Seropositivity and Risk for Interstitial Lung Disease in a Prospective Male-Predominant Rheumatoid Arthritis Cohort of U.S. Veterans

• Published in: Annals of the American Thoracic Society Vol. 18; no. 4; pp. 598 - 605
• Main Authors: Natalini, Jake G., Baker, Joshua F., Singh, Namrata, Mahajan, Tina D., Roul, Punyasha, Thiele, Geoffrey M., Sauer, Brian C., Johnson, Cheilonda R., Kawut, Steven M., Mikuls, Ted R., England, Bryant R.
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.04.2021
• Subjects: Antibodies; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - epidemiology; Cohort Studies; Cross-Sectional Studies; Female; Humans; Lung Diseases, Interstitial - epidemiology; Male; Middle Aged; Original Research; Regression analysis; Retrospective Studies; Rheumatoid arthritis; Risk factors; Veterans; rheumatoid factor; anti–citrullinated protein antibodies; rheumatoid arthritis–associated interstitial lung disease
• ISSN: 2329-6933; 2325-6621; 2325-6621
• DOI: 10.1513/AnnalsATS.202006-590OC

Prior studies investigating associations of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) seropositivity with risk for rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) have mostly used cross-sectional or case-control designs. To determine whether combined autoantibody seropositivity and higher individual autoantibody concentrations were associated with increased risk for RA-ILD in a prospective RA cohort. Within the Veterans Affairs Rheumatoid Arthritis prospective registry, we performed a cross-sectional study of prevalent ILD and a retrospective cohort study of incident ILD (diagnosed after at least 12 mo of longitudinal follow-up). We used logistic and Cox regression methods to determine whether combined RF/ACPA seropositivity and higher autoantibody concentrations were independently associated with greater risk for prevalent and incident ILD, respectively. Among 2,328 participants (median age 64 yr, 89.3% male), 100 (4.3%) subjects had prevalent ILD at enrollment. During 14,281 patient-years of follow-up, 83 (3.7%) of the remaining 2,228 were subsequently diagnosed with incident ILD (5.8 cases per 1,000 person-years). Patients with combined RF/ACPA seropositivity had a higher probability of prevalent ILD compared with seronegative subjects (odds ratio [OR], 2.90; 95% confidence interval [CI], 1.24-6.78). RF titers demonstrated a monotonic association with prevalent ILD (OR, 2.69; 95% CI, 1.11-6.51 for low-positive [15-45 IU/ml] titers; OR, 3.40; 95% CI, 1.61-7.18 for high-positive [>45 IU/ml] titers; for trend 0.01). Patients with high-positive (>15 U/ml) ACPA titers were also at higher risk for prevalent ILD (OR, 1.91; 95% CI, 1.04-3.49) compared with ACPA-negative subjects. Combined RF/ACPA seropositivity was not associated with increased risk for incident ILD, nor were high- or low-positive RF or ACPA titers. In a piecewise linear spline model, however, RF titers greater than 90 IU/ml independently correlated with increased risk for incident ILD (hazard ratio, 1.68, 95% CI, 1.02-2.77). Combined RF/ACPA seropositivity and individual autoantibody concentrations were strongly associated with prevalent but not incident RA-ILD. Only patients with RF concentrations >90 IU/ml were observed to be at higher risk of incident RA-ILD.