Background Current diagnosis of antiphospholipid syndrome (APS) relies on antiphospholipid antibodies (aPL) testing, but false-positive aPL results and asymptomatic aPL carriers pose significant clinical challenges. The importance of S100A8 in thrombosis has been demonstrated, yet its potential role in APS has received little attention. This study aimed to assess serum S100A8 for APS diagnosis and risk stratification among aPL carriers. Methods Serum S100A8 levels were measured by ELISA in healthy controls (HCs), aPL carriers without manifestation and patients with APS. Receiver operating characteristic curves were used to evaluate the diagnostic performance of APS. Logistic regression was performed to identify independent variables associated with obstetric morbidity among female aPL carriers. Results The study enrolled 120 HCs, 57 aPL carriers and 114 patients with APS. Serum S100A8 levels were significantly higher in aPL carriers (median 44.3 (IQR 35.6–75.4) ng/mL, p<0.001) and patients with APS (52.8 (37.2–79.2) ng/mL, p<0.001) compared with HCs (25 (21.6–31.1) ng/mL). S100A8 showed good diagnostic accuracy for APS (area under the curve (AUC)=0.854, 95% CI 0.803 to 0.907, p<0.001), with similar performance for thrombotic APS (AUC=0.819, 95% CI 0.747 to 0.891, p<0.001) and obstetric APS (AUC=0.874, 95% CI 0.821 to 0.926, p<0.001). Multivariate logistic regression revealed that S100A8 positivity was independently associated with increased obstetric APS risk among aPL carriers (OR 3.335, 95% CI 1.010 to 11.012, p=0.048). Conclusion S100A8 may serve as a complementary biomarker for the diagnosis and risk stratification of APS, especially in female aPL carriers at risk of obstetric morbidity. These findings support further investigation into its clinical and mechanistic role in APS pathogenesis.
Luo et al. (Thu,) studied this question.