Clinical relevance of rheumatoid factor and anti‐citrullinated peptides in fibrotic interstitial lung disease Academic Article uri icon

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  • Background and objective

    Rheumatoid arthritis (RA) is a frequent cause of interstitial lung disease (ILD); however, the impact of rheumatoid factor and anti-citrullinated peptide antibody seropositivity in ILD without connective tissue disease (CTD) is unclear. We examined the association of seropositivity with ILD progression, mortality and response to immunosuppression in non-CTD ILD.


    A total of 1570 non-CTD patients (with idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, interstitial pneumonia with autoimmune features or unclassifiable ILD) and 181 RA-ILD patients were included from a prospective registry. Longitudinal forced vital capacity (FVC), transplant-free survival and incidence of progressive fibrosing-ILD (PF-ILD) were compared between seronegative non-CTD ILD (reference group), seropositive non-CTD ILD and RA-ILD using linear mixed-effect and Cox proportional hazards models adjusted for age, sex, smoking pack-years and baseline FVC. Interaction between seropositivity and immunosuppression on FVC decline was assessed in patients with ≥6 months of follow-up before and after the treatment.


    Two hundred and seventeen (13.8%) patients with seropositive non-CTD ILD had similar rates of FVC decline and transplant-free survival compared to seronegative non-CTD ILD, but more frequently met the criteria for PF-ILD (hazard ratio [HR] = 1.35, p = 0.004). RA-ILD had slower FVC decline (p = 0.03), less PF-ILD (HR = 0.75, p = 0.03) and lower likelihood of lung transplant or death (HR = 0.66, p = 0.01) compared to seronegative non-CTD ILD. No interaction was found between seropositivity and treatment on FVC decline in non-CTD ILD.


    Seropositivity in non-CTD ILD was not associated with improved outcomes or treatment response, highlighting the importance of other disease features in determining prognosis and predicting response to immunosuppression.


  • Zheng, Boyang
  • Donohoe, Kathryn
  • Hambly, Nathan
  • Johannson, Kerri A
  • Assayag, Deborah
  • Fisher, Jolene H
  • Manganas, Helene
  • Marcoux, Veronica
  • Khalil, Nasreen
  • Kolb, Martin Rainer
  • Ryerson, Christopher J
  • Wong, Alyson W
  • Lok, Stacey
  • Morisset, Julie
  • Fell, Charlene D
  • Shapera, Shane
  • Gershon, Andrea S
  • Cox, Gerard
  • Halayko, Andrew J
  • Sadatsafavi, Mohsen
  • Wilcox, Pearce G
  • To, Teresa

publication date

  • October 2022