Urinary 8-oxoGuo as a potential novel evaluation biomarker for patients with systemic lupus erythematosus

尿液 8-oxoGuo 作为系统性红斑狼疮患者潜在的新型评估生物标志物

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Abstract

OBJECTIVE: We evaluated the urinary levels of 8-oxo-7,8-dihydroguanosine/creatinine(8-oxoGuo/Cr) and 8-oxo-7,8-dihydroguanosine/specific gravity (8-oxoGuo/SG) as potential biomarkers for diagnosing systemic lupus erythematosus and determining disease activity. METHODS: A total of 160 participants, including 86 patients meeting American College (ACR) criteria for systemic lupus erythematosus (SLE) and 74 control individuals matched for age and gender, were enrolled in the study. Urine RNA oxidation marker 8-oxo-7,8-dihydroguanosine (8-oxoGuo) detected by HPLC-electrochemical and normalized to urine creatinine and specific gravity. SLE disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2000), a widely utilized and scientifically validated clinical assessment tool to measure disease activity in SLE patientsResults: There were significant differences between SLE patients and health controls in terms of serum ALT (P = 0.013), serum TP (P < 0.001), serum ALB (P < 0. 001), TBIL (P < 0. 001), DBIL (P < 0. 001), GLU (P < 0. 001), UREA (P = 0.017), Scr (P = 0.025), and UREA/Scr (P < 0. 001). Important disease indicators of SLE patients were showed in Table 2. Urine concentrations of 8-oxoGuo/Cr and 8-oxoGuo/SG were significantly higher in patients with SLE. In SLE patients, the values of 8-oxoG/Cr were higher at 2.32 ± 1.07 μmol/mol compared to healthy controls at 1.62 ± 0.65 μmol/mol, and the values of 8-oxoG/SG were higher at 2.06(1.63,2.73) pg/μL compared to healthy controls at 1.32(0.68,2.01)pg/μL. The AUCs for 8-oxoGuo/Cr and 8-oxoGuo/SG were both higher than 0.7, they were 0.733 (P < 0.0001) and 0.767 (P < 0.0001), respectively. The 95% confidence interval (CI) for the AUC of 8-oxoGuo/Cr and 8-oxoGuo/SG were 0.656-0.811 and 0.691-0.843, respectively. Higher 8-oxoG/Cr levels in SLE patients were associated with ESR (Spearman's rho = 0.242, P = 0.003) and SLEDAI-2000 score (Spearman's rho = 0.328, P < 0.001). Higher 8-oxoG/SG levels in SLE patients were negative associated with 24H UA (Spearman's rho = - 0.292, P < 0.001) and positive associated with SLEDAI-2000 score (Spearman's rho = 0.195, P < 0.016). Additionally, the levels of 8-oxoGuo/Cr and 8-oxoGuo/SG were significantly higher in disease activity groups of patients with SLE compared to both the control group and patients in remission. CONCLUSIONS: Urine 8-oxoGuo/Cr and 8-oxoGuo/SG could be a potential biomarker associated with severity and disease activity in individuals diagnosed with SLE.

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