Serum Uric Acid as a Potential Biomarker in Patients With Rheumatoid Arthritis-associated Interstitial Pneumonia (RA-ILD)

Abstract

Background: Uric acid (UA) has been reported participate in various inflammatory and autoimmune diseases. Increasing evidence has shown that UA also plays an important role in lung inflammation and fibrosis. We aimed to investigate the correlation between UA and rheumatoid arthritis (RA), especially rheumatoid arthritis-associated interstitial lung disease (RA-ILD).Methods: 266 RA patients and 138 healthy individuals were recruited in this study. RA was identified according to ACR/EULAR 2010 criteria. UA in serum and bronchoalveolar lavage fluid (BALF), as well as clinic and laboratory Indexes were collected from participants enrolled in the study. Serum KL-6 was measured via ELISA and then Spearman correlation analysis was used to analysing their association. Subsequent the receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to estimate the diagnostic value of UA in RA-ILD and UIP pattern of RA-ILD. HRCT and pulmonary function tests (PFT) were performed to evaluated the characteristics and pulmonary findings of RA patients. Furtherly, we validated the effect of UA on the EMT and the expression of cytokines in A549 cells. Results: Compared with healthy controls (HC), UA levels in serum was significantly higher in RA group (262.25±91.94 vs. 234.69±54.78µmol/L, P<0.01). Spearman correlation analysis revealed associations of SUA with risk factors of RA, including RF, anti-CCP, CRP and ESR (r=0.37, p=0.02; r=0.48, p<0.01; r=0.26, p<0.01; r=0.27, p<0.01). And higher UA was measured both in serum (291.81±102.42 vs. 252.38±6.15µmol/L, P<0.01) and BALF (393.3±222.6 vs. 204.0±120.3µmol/L, p<0.01) of RA-ILD patients, particularly those with UIP pattern (475.58±249.28 vs. 262.86±103.45µmol/L, p<0.01; 393.3±222.6 vs. 204.0±120.3µmol/L, p<0.01). Meanwhile, the correlation between the level of UA in serum and BALF and serum KL-6 concentration in RA were also significant (r=0.59, p<0.01; r=0.43, p<0.01). Also, the negative correlations of UA level, both in serum and BALF, with lung function parameters including FEV1/FVC and FEV1% predicted were measured (r=-0.78; r=-0.87, p<0.01). In the ROC curve analysis of AUC, the AUC value of UA was 0.76 (95%CI=0.66-0.87, p<0.01). The sensitivity and specificity were 60% and 92%, respectively. The vitro experiment showed that UA stimulated the EMT in A549 cells, as well as induced the expression of cytokines, such as IL-1, IL-6 and TGF-β, in lung epithelial cell.Conclusions: This study suggests that UA is correlated with the ILD in RA. Particularly, the higher UA levels may be related to UIP, a pattern with worse prognosis, in patients with ILD. Therefore, UA may be an important contributing factor to the pathogenesis of RA-ILD.