Serum Uric Acid as a Diagnostic Biomarker for Rheumatoid Arthritis–Associated Interstitial Lung Disease

Abstract

Previous studies have suggested a correlation between uric acid (UA) and lung lesion in some diseases. 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–associated 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-β (TGF-β) 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 (r = 0.44, p < 0.01; r = 0.43, p < 0.01). And, the negative correlations of UA, in both serum and BALF, with forced vital capacity (r = −0.61, p < 0.01; r = −0.34, p < 0.01) and diffusing capacity for carbon monoxide (r = −0.43, p < 0.01; r = −0.30, p < 0.01) were measured in patients. In the ROC curve analysis, the AUC value of UA for RA-ILD was 0.744 (95% CI: 0.69–0.80; p < 0.01), and the AUC of serum UA for predicting UIP pattern of patients with RA-ILD was 0.845 (95% CI: 0.78–0.91; p < 0.01), 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-β in A549 cells. Therefore, the elevated UA levels may be a diagnostic marker in RA-ILD, particularly RA-UIP.

The Interplay between Cardiovascular Risk, Cardiovascular Events, and Disease Activity in Primary Sjögren’s Syndrome: Is Uric Acid the Missing Link?

“…In more detail, patients with higher SUA levels have a higher prevalence of pulmonary manifestations, namely interstitial lung disease (ILD) and a relationship between pSS-ILD and the occurrence of previous CV events has also emerged. In line with our findings, a recent study demonstrated that patients with ILD associated with RA display higher levels of SUA and also higher levels of bronchoalveolar lavage fluid (BALF)-UA [ 27 ]. A study using an experimental model of ILD demonstrated that bleomycin-induced lung injury triggers local production of UA, thereby activating the NALP3 inflammasome in the lung and perpetuating lung damage [ 28 ].…”

“…A study using an experimental model of ILD demonstrated that bleomycin-induced lung injury triggers local production of UA, thereby activating the NALP3 inflammasome in the lung and perpetuating lung damage [ 28 ]. In addition, higher SUA and BALF-UA levels have been associated with worse pulmonary function at spirometry not only in RA-ILD but also in healthy subjects [ 27 , 29 ].…”

Unmet needs and perspectives in rheumatoid arthritis-associated interstitial lung disease: A critical review

“…Among tests usually performed in the clinical setting, an unsuspected role has been proposed for serum uric acid, for which higher levels were observed in RA-ILD with a prevailing UIP pattern at HRCT ( 116 ). Serum uric acid is already included in the DETECT algorithm for early detection of pulmonary arterial hypertension in patients with systemic sclerosis (SSc) ( 117 ).…”

A Systematic Review and Meta-Analysis of the Association between Uric Acid and Allantoin and Rheumatoid Arthritis

“…A total amount of 1694 was excluded after the initial screening because of duplication or irrelevance to the search question. After reviewing the full text of the remaining 24 articles, a further five were removed because they failed to meet the inclusion criteria, leaving 19 studies, published between 1987 and 2022, for analysis (Tables 1 and S3) [63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81]. Legend: F, female; M, male; NR, not reported; *, µmol/L; • , mmol/L.…”