Increased Serum Concentration of Sphingosine-1-phosphate in Juvenile-onset Systemic Lupus Erythematosus

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Abstract
Purpose Sphingosine-1-phosphate (S1P) is an active sphingolipid with chemotactic abilities and has been linked to inflammatory mediators and autoimmune disease. The aim of this study was to assess whether children with juvenile-onset systemic lupus erythematosus (JSLE) express increased systemic and/or urinary concentrations of S1P. Methods A subgroup of patients participating in the UK JSLE Cohort Study, were invited to participate. Cross sectional serum and urine samples were prospectively collected along with demographic and standard clinical data. Results were compared to a cohort of disease controls (Henoch Schonlein Purpura; HSP) and healthy controls (HC). Results The median age of JSLE patients (n = 15) was 13.6 years (7.2–16.9 years). The serum concentrations of S1P in JSLE patients (7.4 uM, IQR 6.3–12.3 uM) were statistically significantly increased when compared to patients with HSP (n = 10; 5.2 uM, IQR 4.0–7.9 uM; p = 0.016) and HCs (n = 10; 3.8 uM, IQR 2.1–5.8 uM; p = 0.003). There was a trend towards increased serum S1P concentrations between patients with active lupus nephritis (n = 8; 8.7 uM, IQR 6.2–15.3 uM) compared to lupus non-nephritis (n = 7; 6.6 uM, IQR 6.3–10.6 uM; p = 0.355). No relationship was found between disease activity markers and S1P. Urine S1P concentrations were no different between JSLE patients (56.0 nM, IQR 40.3–96.6 nM) and HCs (58.7 nM, IQR 0–241.9 nM; p = 0.889). Conclusions We have demonstrated, for the first time, an increased serum concentration of S1P in a cohort of JSLE patients. These findings highlight a role of S1P in the pathophysiology of JSLE that warrants further investigation.

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