S100A8 in Serum, Urine, and Saliva as a Potential Biomarker for Systemic Lupus Erythematosus

Abstract

Objectives: This study aimed to elucidate the potential of serum, urine, and saliva S100 calcium-binding protein A8 protein (S100A8) levels as biomarkers for systemic lupus erythematosus (SLE).

Methods: Serum, urine, and saliva samples were obtained from 249 patients with SLE from the Ajou lupus cohort and 52 age- and sex-matched healthy controls (HCs). The concentrations of S100A8 were quantified using an ELISA, and a receiver operating characteristic curve was used to analyze whether they may be used as biomarkers for diagnosing SLE.

Results: Among 249 SLE patients included in our study, the mean SLE disease activity index (SLEDAI)-2K was 7.16 ± 5.61, and the number of patients with lupus flare was 11. Patients with SLE showed a 2.7-fold increase in serum S100A8 levels compared with that in HCs (1,890.6 vs. 709 pg/ml, p < 0.001). In urine and saliva, the average S100A8 levels were significantly higher in patients with SLE compared with those in HCs (urine, 2,029.4 vs. 1,096.7 pg/ml, p = 0.001; saliva, 290,496.3 vs. 47,742 pg/ml, p < 0.001). For SLE diagnosis, the area under the receiver operating characteristic curve was 0.831 for serum S100A8 (95% CI, 0.765-0.897), 0.751 for urine S100A8 (95% CI, 0.648-0.854), and 0.729 for salivary S100A8 (95% CI, 0.646-0.812). Pearson's correlation analysis showed that S100A8 in serum, urine, and saliva was significantly associated with the SLEDAI (r = 0.267, p < 0.001; r = 0.274, p < 0.001; and r = 0.629, p < 0.001, respectively). Among the clinical manifestations, nephritis was the most influential factor related to SLE in the concentration of S100A8 in serum, urine, and saliva.

Conclusion: This is the first study to show that the expression of S100A8 in serum, urine, and saliva is significantly higher in patients with SLE than in HCs and is associated with disease activity markers. Therefore, we suggest that S100A8 protein could be a potential biomarker for SLE.

Keywords: S100A8; biofluids; biomarkers; disease activity; systemic lupus erythematosus.

Figure 1

(A) Serum level of S100A8 in patients with systemic lupus erythematosus (SLE). (B) Urine level of S100A8 in patients with SLE. (C) Salivary level of S100A8 in patients with SLE. Central horizontal bar indicates mean value. Statistical analyses were conducted using Mann–Whitney U test.

Figure 2

Receiver operating characteristic curves associated with the diagnostic utility of S100A8 in serum, urine, and saliva. For SLE diagnosis, the AUC was 0.831 for the serum S100A8 (95% CI, 0.765–0.897), 0.751 for the urine S100A8 (95% CI, 0.648–0.854), and 0.729 for the salivary S100A8 (95% CI, 0.646–0.812). AUC, area under the receiver operating characteristic curve; SLE, systemic lupus erythematosus.

Figure 3

Scatter plots showing positive correlations between S100A8 and SLEDAI-2K in patients with SLE. (A) Serum S100A8. (B) Urine S100A8. (C) Salivary S100A8. SLEDAI, systemic lupus erythematosus (SLE) disease activity index. Statistical analyses were conducted using Pearson’s correlation analyses.