P40 S100A8/A9 and S100A12 may be biomarkers for juvenile-onset systemic lupus erythematosus
Authors: Donohue Sean Joseph , Midgley Angela , Bruce Ian , Beresford Michael W , Hedrich Christian M 
Published: October 2019

Abstract

Background
Juvenile-onset SLE (JSLE) is a systemic autoimmune disease affecting young people before the age of 17 years. Despite recent progress in understanding the pathogenesis of JSLE, it remains unclear. The lack of reliable biomarkers makes the assessment of disease activity and organ involvement challenging. A family of pro-inflammatory molecules known as S100 proteins have recently emerged as potential biomarkers for monitoring disease activity in an adult-onset SLE and various (auto-) inflammatory conditions. We investigated the usefulness of S100A8/A9 and S100A12 serum and urine levels as biomarkers for renal involvement and/or disease activity in JSLE.

Methods
Serum and urine from JSLE patients (n = 60), matched healthy controls (n = 53) and patients with IgA vasculitis (disease controls, n = 9) were collected. S100A8/A9 and S100A12 concentrations in serum and urine samples were quantified using the Meso Scale Discovery Immunoassay [serum; median ng/mL (I.Q.R), urine; median ng/mmol creatinine (I.Q.R)]. Furthermore, S100 protein concentrations in serum and urine were compared between groups and between JSLE patients with active (BILAG scores A, B, C) and inactive (BILAG scores D, E) renal disease. Potential effects of age, sex and global disease activity (SLEDAI scores) on S100 protein concentrations were tested.

Results
S100A8/A9 levels were significantly increased in the serum of JSLE patients [1577.80ng/mL (2313.97)] when compared to healthy controls [732.53 ng/mL (1003.47); p < 0.001)] and patients with IgA vasculitis [531.23 ng/mL (824.50); p < 0.05)]. This, however, was not reflected in patients’ urine samples. S100A12 concentrations were significantly increased in both the serum [41.12 ng/mL = (106.06); p < 0.05] and urine [90.12ng/mmol creatinine (348.44); p < 0.05] when compared to healthy controls [serum;17.75ng/mL(47.16), urine; 14.88ng/mmol creatinine (198.36)]. No differences were seen between S100A12 protein levels in serum or urine of JSLE patients when compared to patients with IgA vasculitis. No differences were observed between S100 protein concentrations in the serum or urine of patients with JSLE with active vs. inactive renal disease, between ages or sexes. Also, global disease activity (SLEDAI) did not correlate with serum or urine S100 protein concentrations.

Conclusion
JSLE patients exhibit increased concentrations of S100A8/A9 and S100A12 proteins in the serum, independent of clinical disease activity. Furthermore, increased urine concentrations of S100A12 in JSLE patients are independent of current renal involvement or activity.
Based on the small molecular weight of S100 proteins, this may suggest renal loss of elevated serum S100A12 (21 kDa) through the kidneys rather than being the result of kidney inflammation or damage. Thus, S100 proteins may help to distinguish JSLE patients from healthy controls and patients with the differential diagnosis IgA vasculitis, supporting previous reports in adult-onset SLE. Longitudinal assessment of S100 proteins for an individual patient and/or in combination with other biomarkers may be helpful in assessing disease activity in JSLE patients.

Conflicts of Interest
The authors declare no conflicts of interest.