Clinical relevance of rheumatoid factor and anti-citrullinated peptides in fibrotic interstitial lung disease

Boyang Zheng; Kathryn Donohoe; Nathan Hambly; Kerri A Johannson; Deborah Assayag; Jolene H Fisher; Helene Manganas; Veronica Marcoux; Nasreen Khalil; Martin Kolb; Christopher J Ryerson; CARE-PF Investigators

doi:10.1111/resp.14301

Clinical relevance of rheumatoid factor and anti-citrullinated peptides in fibrotic interstitial lung disease

Respirology. 2022 Oct;27(10):854-862. doi: 10.1111/resp.14301. Epub 2022 Jun 2.

Authors

Collaborators

CARE-PF Investigators:
Alyson W Wong, Stacey Lok, Julie Morisset, Charlene D Fell, Shane Shapera, Andrea S Gershon, Gerard Cox, Andrew J Halayko, Mohsen Sadatsafavi, Pearce G Wilcox, Teresa To

Affiliations

¹ Division of Rheumatology, McGill University, Montreal, Quebec, Canada.
² Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
³ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁴ Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
⁵ Department of Medicine, McGill University, Montreal, Quebec, Canada.
⁶ Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
⁸ Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
⁹ Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada.

PMID: 35652240
DOI: 10.1111/resp.14301

Abstract

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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: anti-citrullinated peptide; autoantibody; immunosuppression; interstitial lung disease; prognosis; pulmonary fibrosis; rheumatoid factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid* / complications
Connective Tissue Diseases* / complications
Humans
Idiopathic Pulmonary Fibrosis* / complications
Lung
Lung Diseases, Interstitial* / etiology
Peptides / therapeutic use
Rheumatoid Factor

Substances

Peptides
Rheumatoid Factor