Clinical Interpretation of Platelet Activation Marker sCLEC-2 in Antiphospholipid Syndrome

Soluble C-type lectin-like receptor 2 (sCLEC-2) has emerged as a biomarker of platelet activation and thrombus formation. Antiphospholipid syndrome (APS) is characterized by arterial and venous thrombosis and pregnancy complications, driven in part by platelet activation. However, the clinical utility of sCLEC-2 and the sCLEC-2/D-dimer ratio in APS remains unclear.

Plasma samples from 19 patients with primary APS, 30 with SLE-associated APS, 10 with SLE without APS, 40 with other collagen diseases, and 40 healthy controls (n = 139) were analyzed. Plasma sCLEC-2 levels and D-dimer levels were quantified by immunoassay. Antiphospholipid antibodies (anti-cardiolipin antibodies and anti-β₂-glycoprotein I antibodies IgG/IgM) were measured by ELISA kits. Group comparisons and correlations were evaluated.

Using the upper limit of the 95% CI of healthy controls as a cutoff, sCLEC-2 positivity was observed in 100% of non-APS autoimmune disease patients, and 98.0% of APS patients. sCLEC-2, D-dimer, and the sCLEC-2/D-dimer ratio were significantly higher in non-APS and APS groups compared with controls (p < 0.001). A slight but significant difference in the sCLEC-2 and the ratio was observed between the non-APS and APS groups. However, no significant differences were found among APS subgroups stratified by thrombosis type. sCLEC-2 showed no correlation with any of four major antiphospholipid antibody titers.

Although we observed raised sCLEC-2 and sCLEC-2/D-dimer ratio among APS and non-APS groups and modest differences between the two groups, clinical interpretation of the findings requires a prospective study evaluating dynamic changes of sCLEC-2 in the clinical course.