Arthritis care & research · 2026
Combining Three Peripheral Blood Biomarkers to Stratify Rheumatoid Arthritis-Associated Interstitial Lung Disease Risk.
СтатьяМногоцентровое исследованиеНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Coziahr Kelsey, Wheeler Austin M, Luedders Brent A, Duryee Michael, Frideres Halie, Wysham Katherine D, Cannon Grant W, Kunkel Gary, Ascherman Dana P, Monach Paul A, Kerr Gail S, Reimold Andreas M, Matson Scott M, Baker Joshua F, Thiele Geoffrey M, Mikuls Ted R, England Bryant R
Аннотация
OBJECTIVE: The purpose was to evaluate a biomarker score consisting of MUC5B rs35705950 promoter variant, plasma matrix metalloproteinase-7 (MMP-7), and serum anti-malondialdehyde-acetaldehyde (anti-MAA) antibody for rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) risk stratification.
METHODS: Using a multicenter cohort of US veterans with RA, we performed a cross-sectional study of prevalent RA-ILD and a cohort study of incident RA-ILD. Medical records were used to confirm clinical ILD diagnoses by chest imaging or lung biopsy pathology reports. A combined three-biomarker score (range 0-3) was calculated based on the presence of the MUC5B variant and elevations (upper 25% vs lower 75%) in MMP-7 and anti-MAA antibody concentrations. Multivariate logistic and Cox regression models were adjusted for clinical risk factors.
RESULTS: Among 2,043 participants with RA, prevalent ILD was identified in 88 (88.7% male; mean age 63.6 years). The odds of prevalent RA-ILD were higher with increased biomarker score (adjusted odds ratio 12.21 [95% confidence interval (CI) 3.82-38.97] for score of 3 vs 0). A score ≥1 had 76.1% sensitivity but 48.6% specificity. Incident RA-ILD developed in 148 participants, with those having a combined biomarker score of 3 having the highest risk (adjusted hazard ratio 4.36 [95% CI 1.55-12.27]). The area under the curve for prevalent RA-ILD and Harrell's C for incident RA-ILD were highest when clinical risk factors were combined with the biomarker score.
CONCLUSION: This three-analyte biomarker score was associated with both prevalent and incident RA-ILD, improving risk stratification beyond clinical risk factors. Although this score is inadequate for clinical implementation, these findings demonstrate the potential for biomarker scores in RA-ILD risk stratification.
METHODS: Using a multicenter cohort of US veterans with RA, we performed a cross-sectional study of prevalent RA-ILD and a cohort study of incident RA-ILD. Medical records were used to confirm clinical ILD diagnoses by chest imaging or lung biopsy pathology reports. A combined three-biomarker score (range 0-3) was calculated based on the presence of the MUC5B variant and elevations (upper 25% vs lower 75%) in MMP-7 and anti-MAA antibody concentrations. Multivariate logistic and Cox regression models were adjusted for clinical risk factors.
RESULTS: Among 2,043 participants with RA, prevalent ILD was identified in 88 (88.7% male; mean age 63.6 years). The odds of prevalent RA-ILD were higher with increased biomarker score (adjusted odds ratio 12.21 [95% confidence interval (CI) 3.82-38.97] for score of 3 vs 0). A score ≥1 had 76.1% sensitivity but 48.6% specificity. Incident RA-ILD developed in 148 participants, with those having a combined biomarker score of 3 having the highest risk (adjusted hazard ratio 4.36 [95% CI 1.55-12.27]). The area under the curve for prevalent RA-ILD and Harrell's C for incident RA-ILD were highest when clinical risk factors were combined with the biomarker score.
CONCLUSION: This three-analyte biomarker score was associated with both prevalent and incident RA-ILD, improving risk stratification beyond clinical risk factors. Although this score is inadequate for clinical implementation, these findings demonstrate the potential for biomarker scores in RA-ILD risk stratification.