Multimarker profiling of immune and vascular disregulation in antiphospholipid syndrome and systemic lupus erythematosus

Background Antiphospholipid syndrome (APS) is an autoimmune condition marked by thrombosis and pregnancy complications caused by antiphospholipid antibodies (aPL). This study evaluates immunological, inflammatory, and endothelial biomarkers in primary and secondary APS and SLE to determine their association with clinical outcomes. Material and methods We conducted a cross-sectional study including patients with primary (PAPS) ( n = 79), secondary (SAPS) ( n = 47), SLE ( n = 36), and control group ( n = 56). Serum and plasma samples were analyzed for aPLs, inflammatory markers (hs-CRP, IL-6), endothelial markers (endoglin), platelet activation (CD41/CD61), tissue factor, and iron metabolism markers (hepcidin, ferritin, UIBC) using ELISA and automated assays. Statistical analyses included group comparisons, correlations, multivariate logistic regression analysis and principal component analysis (PCA). Results Non-criteria aPLs, were significantly elevated in all patient groups compared to controls ( p < 0.001). Patients with SAPS demonstrated significantly higher levels of aCL IgG, aCL IgA, aβ2GPI IgM, and aPS/PT (IgG and IgM) compared to PAPS. Strong correlations were identified between aPS/PT IgG and the lupus anticoagulant ratio (LAR) (r = 0.670, p < 0.001), as well as between aβ2GPI IgG and LAR (r = 0.625, p < 0.001). Multivariate logistic regression identified that endoglin and ferritin were independently associated with clinical manifestations. For fetal loss, the model was statistically significant (χ 21 = 16.18, p = 0.013); an increase in endoglin raised the probability by 45.1% (OR = 1.451, p = 0.040), while lower ferritin levels were also independently associated ( p = 0.004). Ferritin showed the strongest independent association with thrombosis (χ 21 = 19.87, p = 0.011), with each unit increase raising the probability of a thrombotic event by 1.5% (OR = 1.015). PCA identified two main factors explaining 63% of the variance: an “Immunological-related” factor (42.96%) dominated by aCL IgG, aβ2GPI IgG, aPS/PT IgG, and aCL IgA, and a “Prothrombotic and metabolic-related” factor (20.06%) driven by aβ2GPI IgM, tissue factor, aCL IgA, and inversely by UIBC. Conclusion The study highlights the interplay of immune, inflammatory, and endothelial dysfunction biomarkers in APS and their association with clinical manifestations. Combined assessment of conventional and non-criteria biomarkers may improve understanding of disease mechanisms and support a more comprehensive evaluation of patients with APS.