Role of the S1P/S1PR axis in inflammation and structural damage in psoriatic arthritis: a cross-sectional study with...

Psoriatic arthritis (PsA) is a chronic inflammatory disease with a complex clinical spectrum. Sphingosine-1-phosphate (S1P) and its receptor (S1PR) are key lipid mediators involved in immunity and bone remodelling. This study evaluates the inter-relationship between serum levels of S1P and S1PR and clinical activity, radiological findings and different stages of PsA.

A cross-sectional observational study was conducted including 64 subjects: 21 healthy controls and 43 patients with PsA: 16 with recent-onset PsA and 27 with established PsA (EPsA). Clinical variables such as disease activity in PsA (DAPSA), bone mineral density (BMD), Trabecular Bone Score, 3D-Shaper and inflammatory activity by Doppler ultrasound and MRI were assessed. S1P and S1PR levels were measured by ELISA.

S1P levels were significantly higher in the PsA group compared with controls (p=0.013), with the highest values observed in the EPsA subgroup (p=0.009). Although no significant correlation was observed with the DAPSA Score, S1PR levels were significantly higher in patients with Achilles enthesitis detected by ultrasound (p=0.046) and in those with bone proliferation/structural damage (p=0.03). Patients with EPsA showed significantly higher cortical volumetric BMD compared with controls (p=0.027).

The S1P/S1PR axis is dysregulated in PsA and is associated with disease progression. Its correlation with ultrasound findings of enthesitis and new bone formation suggests that S1P acts as a critical mediator in the osteoimmunology of the enthesis, positioning it as a potential biomarker of structural damage and a novel therapeutic target.