ABSTRACT
Anti-cyclic citrullinated peptide antibody testing is used to diagnose rheumatoid arthritis and associated with interstitial lung disease in RA. Herein, we investigate the relationship between anti-CCP antibody and ILD in SSc. We performed a retrospective analysis at a tertiary medical center between 2005 and 2019. Patients with SSc, systemic lupus erythematosus, and polymyositis/dermatomyositis (PM/DM) were evaluated for anti-CCP antibody and ILD. Additionally, medical records of SSc patients with ILD were reviewed. SSc patients had the highest anti-CCP antibody positivity rate compared to those with SLE and PM/DM. The incidence of ILD was higher in SSc patients with anti-CCP antibody than in those without. The usual interstitial pneumonia (UIP) incidence was higher in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. The DLCO was lower in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. On multivariable analysis, factors associated with SSc-ILD were anti-CCP antibody or rheumatoid factor (ß coefficient, 2.652 [95% CI 1.472 to 4.776]) and anti-Scl70 antibody (ß coefficient, 4.011 [95% CI 2.142 to 7.508]). Anti-CCP antibody may be associated with a higher incidence of ILD in SSc. SSc patients with anti-CCP antibody may have more UIP pattern and lower DLCO.Trial Registration Retrospectively registered.
Subject(s)
Lung Diseases, Interstitial , Lupus Erythematosus, Systemic , Scleroderma, Systemic , Humans , Anti-Citrullinated Protein Antibodies , Autoantibodies , Lung Diseases, Interstitial/etiology , Lupus Erythematosus, Systemic/epidemiology , Peptides, Cyclic , Retrospective Studies , Rheumatoid Factor , Scleroderma, Systemic/diagnosisABSTRACT
OBJECTIVE: Exaggerated neutrophil activation and formation of neutrophil extracellular traps (NETs) are linked to inflammation and autoimmunity, including rheumatoid arthritis (RA). However, whether NETs are present in the circulation of RA patients and contribute to inflammation and disease progression has not been carefully addressed. We undertook this study to assess markers of neutrophil activation and NET formation in plasma samples, investigating whether they add clinical value in improving the determination of prognosis and monitoring in RA patients. METHODS: Markers of neutrophil activation (calprotectin) and cell death (NETs) were analyzed, using enzyme-linked immunosorbent assay, in serum and plasma obtained from patients in 3 cross-sectional RA cohorts and sex-matched healthy controls. A longitudinal inception cohort (n = 247), seen for a median follow-up of 8 years, was used for predictive analyses. RESULTS: Markers of neutrophil activation and cell death were increased in RA patients compared to healthy individuals (P < 0.0001). Calprotectin levels correlated with the Clinical Disease Activity Index (r = 0.53, P < 0.0001) and could be used to distinguish between patients with disease in remission and those with active disease, an observation not seen when examining C-reactive protein levels. A biomarker panel consisting of anti-citrullinated protein antibody and calprotectin could predict erosive disease (odds ratio [OR] 7.5, P < 0.0001) and joint space narrowing (OR 4.9, P = 0.001). NET levels were associated with markers of inflammation (P = 0.0002). Furthermore, NETs and a "neutrophil activation signature" biomarker panel had good predictive value in identifying patients who were developing extraarticular nodules (OR 5.6, P = 0.006). CONCLUSION: Neutrophils undergo marked activation and cell death in RA. Neutrophil biomarkers can provide added clinical value in the monitoring and prognosis of RA patients and may allow for early preventive treatment intervention.
