Abstract / Summary
Background The 2023 ACR/EULAR antiphospholipid syndrome (APS) classification criteria define a clinical domain characterized mainly by microvascular thrombosis formation and is associated with complement activation. Objective We aimed to evaluate the relationship between the complement profile and organ-specific manifestations of APS, especially microvascular APS (MAPS). Methods Patients fulfilled the 2023 ACR/EULAR APS classification criteria were enrolled. Plasma levels of complement components (Ba, Bb, C3a, C4a, C5a, soluble C5b-9, factor H, factor I, C1q, C2, C3, C4, C5, factor D and factor P) were quantified by chemiluminescent multiplex enzyme-linked immunosorbent assays. Cluster analysis was performed to identify distinct complement activation profiles among clinical subgroups. Results A total of 58 patients with APS, including 51 patients with MAPS consecutively enrolled between August 2023 and June 2025, and 20 healthy controls (HCs) were included in the study. Compared with HCs, patients with MAPS had significantly higher plasma levels of Ba, C3a, C4a, and sC5b-9, and significantly lower levels of C1q, C2, and factor P (all P < 0.05). Cluster analysis identified three subgroups: cluster 1 characterized by predominant MAPS manifestations with marked alternative pathway activation; cluster 2 enriched for myocardial disease and antinuclear antibody positivity, showing predominance of classical and lectin pathway activation; and cluster 3 characterized by macrovascular thrombosis with relatively mild complement activation. A predictive model combining factor P and C3a demonstrated good performance for MAPS (AUC = 0.898; sensitivity 82.4%; specificity 88.9%). Conclusions Complement profiling may serve as a valuable tool for early identification of MAPS, disease monitoring, and guiding individualized treatment, highlighting the potential of complement-targeted therapies in MAPS.