TY - JOUR
T1 - Autoantibody seropositivity and risk for interstitial lung disease in a prospective male-predominant rheumatoid arthritis cohort of U.S. veterans
AU - Natalini, Jake G.
AU - Baker, Joshua F.
AU - Singh, Namrata
AU - Mahajan, Tina D.
AU - Roul, Punyasha
AU - Thiele, Geoffrey M.
AU - Sauer, Brian C.
AU - Johnson, Cheilonda R.
AU - Kawut, Steven M.
AU - Mikuls, Ted R.
AU - England, Bryant R.
N1 - Funding Information:
Supported by the National Heart, Lung, and Blood Institute, grant numbers T32HL007891 (J.G.N.) and K24HL103844 (S.M.K.), the VA Clinical Science Research and Development Merit Award, grant number CX001703 (J.F.B.), a Rheumatology Research Foundation Scientist Development Award (B.R.E.), and the National Institute of General Medical Sciences, grant number U54GM115458 (T.R.M. and B.R.E.).
Publisher Copyright:
Copyright © 2021 by the American Thoracic Society
PY - 2021/4
Y1 - 2021/4
N2 - Rationale: 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. Objectives: To determine whether combined autoantibody seropositivity and higher individual autoantibody concentrations were associated with increased risk for RA-ILD in a prospective RA cohort. Methods: 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. Results: 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; P 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). Conclusions: 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.
AB - Rationale: 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. Objectives: To determine whether combined autoantibody seropositivity and higher individual autoantibody concentrations were associated with increased risk for RA-ILD in a prospective RA cohort. Methods: 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. Results: 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; P 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). Conclusions: 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.
KW - Anti-citrullinated protein antibodies
KW - Rheumatoid arthritis-associated interstitial lung disease
KW - Rheumatoid factor
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U2 - 10.1513/AnnalsATS.202006-590OC
DO - 10.1513/AnnalsATS.202006-590OC
M3 - Article
C2 - 33026891
AN - SCOPUS:85103514767
VL - 18
SP - 598
EP - 605
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
SN - 2325-6621
IS - 4
ER -