Article Text
Abstract
Introduction The S100 proteins are important regulators of diverse calcium-dependent cellular processes including growth regulation, migration and apoptosis. Dysregulated expression of multiple members of S100 family is a common feature of cancer and several autoimmune diseases.
Objectives The aim of this study was to examine whether circulating levels of S100A4, S100A8/9 and S100A12 proteins could be useful as diagnostic or activity specific markers in systemic lupus erythematosus (SLE).
Methods S100 plasma levels were measured by ELISA in a cohort study of 44 patients with SLE, 8 patients with incomplete SLE (iSLE) and 43 healthy controls (HCs). Disease activity was assessed using SLEDAI-2 K. We examined cross sectional associations between concentrations of S100 proteins and SLE status, SLEDAI-2 K scores, and levels of conventional biomarkers.
Results Plasma levels of all analysed S100 proteins (S100A4, S100A8/9 and S100A12) were significantly higher in SLE patients compared to HCs (p<0.001, p<0.01, p<0.001, respectively). In iSLE patients, the levels of S100A4 and S100A12 but not S100A8/9 were significantly higher compared to HCs (p<0.001, p<0.05, p=ns, respectively). ROC curve analysis was performed to establish the optimal threshold to discriminate SLE patients from HCs based on S100 levels. At the optimal cutoff point of 238 ng/ml, the area under curve (AUC) for S100A4 was 0–990 (95% CI: 0.977 to 1.000, p<0.001) with a sensitivity of 96% and specify of 93.0%. The remaining two proteins also showed significant, but not as strong discriminative value [S100A8/9: AUC 0.684 (95% CI: 0.572 to 0.795, p<0.05); S100A12: AUC 0.809 (95% CI: 0.719 to 0.898, p<0.001]. We found that only S100A12 levels were significantly associated with the SLEDAI-2K score (r=0.318, p=0.035). Both S100A8/9 and S100A12 levels were significantly higher in SLE patients with arthritis (p=0.043, p=0.015, respectively) and with haematological features (p=0.002 for both). There were no other significant associations between S100 levels and other conventional markers such as C3, C4 and the anti-dsDNA antibodies.
Conclusions We demonstrate increased S100 proteins expression in SLE patients. Although they were not strongly associated with disease activity, S100 proteins and namely S100A4 could be proposed as a diagnostic biomarker for SLE.
Acknowledgements MHCR for conceptual development of research organisation 00023728 and SVV 260 373.
Disclosure of interest None declared