Exploratory Pilot Study on the Serum Ceramide (16:0) to Sphingosine-1-Phosphate Ratio as a Potential Indicator of Lupus Nephritis and Disease Activity

Sphingolipids are essential for cellular structure and signaling, and recent evidence implicates them in chronic inflammation. We hypothesized that altered sphingolipid metabolism contributes to the disease activity of systemic lupus erythematosus (SLE). Serum sphingolipids were quantified by liquid chromatography-tandem mass spectrometry in 38 female SLE patients (11 with lupus nephritis [LN], 27 without LN) and 30 age-matched healthy controls (HCs). Serum ceramide (Cer)16/sphingosine-1-phosphate (S1P) ratios were elevated in SLE compared to HCs (0.33 [0.26-0.38] vs. 0.25 [0.21-0.3], <i>p</i> = 0.019). Notably, Cer16/S1P levels were significantly higher in the LN group (0.33 [0.26-0.38]) than in non-LN SLE (0.27 [0.2-0.34], <i>p</i> = 0.027). ROC analysis showed good diagnostic potential for LN (AUC = 0.739). Cer16/S1P correlated positively with disease activity markers, including erythrocyte sedimentation rate (r = 0.519, <i>p</i> = 0.001), SLE Disease Activity Index 2000 (SLEDAI-2k) score (r = 0.547, <i>p</i> < 0.001), anti-double stranded DNA antibody levels (r = 0.359, <i>p</i> = 0.027), and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (r = 0.327, <i>p</i> = 0.045). The serum Cer16/S1P ratio may serve as a surrogate marker of disease activity in patients with LN.