Objective: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a relatively common extra-articular manifestation of RA that contributes significantly to disease burden and excess mortality.Peripheral blood biomarkers of RA-ILD are therefore needed to facilitate earlier diagnosis and to provide insight regarding pathogenesis of this potentially devastating disease complication.Methods: Subjects with RA that were enrolled into a well characterized Chinese identification cohort and a US replication cohort were subclassified as RA-no ILD, RA-mild ILD, and RA-established ILD based on high resolution computed tomography scans of the chest.Multiplex ELISAs employing Luminex xMAP technology were used to assess 37 cytokines/chemokines, matrix metalloproteinases, and acute-phase proteins in the identification cohort.Quantitative sandwich ELISas for MMP7 and I P10/CXCL10 were then used to confirm results from both the identification and replication cohorts.Unadjusted and adjusted logistic regression models quantified the strength of association between RA-ILD and biomarkers of interest.Results: Multiplex ELISAs identified IP10/CXCL10 and MMP-7 as potential biomarkers of RA-ILD in 133 Chinese RA patients (n=50 RA-no ILD, n=41 RA-ILD, n=42 RA-indeterminate ILD).Standard solid phase sandwich ELISAs confirmed these findings in the Chinese identification cohort as well as an independent US cohort of patients with different stages of RA-ILD (n=22 RA-no ILD, n=49 RA-ILD, and n=13 RA-indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analysis.Conclusion: IP10/CXCL10 and MMP-7 are elevated in the serum of patients with different stages of RA-ILD, demonstrating their potential value as diagnostic biomarkers permitting earlier, non-invasive detection of this extra-articular disease complication.