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However, it remains unknown whether UA contributes to the lung injury in rheumatoid arthritis (RA). Our study aimed to investigate the clinical value of the UA level in the severity of rheumatoid arthritis\u2013associated interstitial lung disease (RA-ILD). We measured UA in serum and bronchoalveolar lavage fluid (BALF), and UA levels of subjects were compared. As for the role of UA on ILD, we incubated A549 cells with UA and the expression of EMT markers was measured by immunofluorescence staining. The concentrations and messenger RNA expression of IL-1, IL-6, and transforming growth factor-\u03b2 (TGF-\u03b2) were measured by ELISA and RT-PCR, respectively. We observed that serum UA levels in RA were significantly higher than those in controls. And, higher UA was measured in both serum and BALF of patients with RA-ILD, particularly those with interstitial pneumonia (UIP) pattern. Additionally, the correlation of the serum and BALF UA levels with serum KL-6, a biomarker of ILDs, in RA was significant (<jats:italic>r<\/jats:italic>\u2009=\u20090.44, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01; <jats:italic>r<\/jats:italic>\u2009=\u20090.43, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). And, the negative correlations of UA, in both serum and BALF, with forced vital capacity (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2009\u22120.61, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01; <jats:italic>r<\/jats:italic>\u2009=\u2009\u2009\u22120.34, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and diffusing capacity for carbon monoxide (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2009\u22120.43, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01; <jats:italic>r<\/jats:italic>\u2009=\u2009\u2009\u22120.30, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) were measured in patients. In the ROC curve analysis, the AUC value of UA for RA-ILD was 0.744 (95% CI: 0.69\u20130.80; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), and the AUC of serum UA for predicting UIP pattern of patients with RA-ILD was 0.845 (95% CI: 0.78\u20130.91; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), which showed the significance of the UA in clinical settings. Also, the in vitro experiment showed that UA induced epithelial-to-mesenchymal transition (EMT) and production of IL-1, IL-6, and TGF-\u03b2 in A549 cells. Therefore, the elevated UA levels may be a diagnostic marker in RA-ILD, particularly RA-UIP.<\/jats:p>","DOI":"10.1007\/s10753-022-01661-w","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T01:04:47Z","timestamp":1647911087000},"page":"1800-1814","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Serum Uric Acid as a Diagnostic Biomarker for Rheumatoid Arthritis\u2013Associated Interstitial Lung Disease"],"prefix":"10.1007","volume":"45","author":[{"given":"Zitao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangdong","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8536-9522","authenticated-orcid":false,"given":"Jianmin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"issue":"3","key":"1661_CR1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.immuni.2013.12.015","volume":"40","author":"K Neumann","year":"2014","unstructured":"Neumann, K., M. 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Andreozzi, G.C. Mannino, and G. Sesti. 2017. Uric acid is associated with inflammatory biomarkers and induces inflammation via activating the NF-kappaB signaling pathway in HepG2 cells. Arteriosclerosis, Thrombosis, and Vascular Biology 37 (6): 1241\u20131249.","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"1661_CR4","doi-asserted-by":"crossref","unstructured":"Lyngdoh, T., P. Marques-Vidal, F. Paccaud, M. Preisig, G. Waeber, M. Bochud, P. Vollenweider. 2011. Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study. PLoS One 6(5):e19901.","DOI":"10.1371\/journal.pone.0019901"},{"key":"1661_CR5","doi-asserted-by":"crossref","unstructured":"Conforti-Andreoni, C., R. Spreafico, H.L. Qian, N. Riteau, B. Ryffel, P. Ricciardi-Castagnoli, and A. Mortellaro. 2011. Uric acid-driven Th17 differentiation requires inflammasome-derived IL-1 and IL-18. 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