Cytokine profiling reveals distinct inflammatory clusters and clinical correlations in antiphospholipid syndrome

Inflammatory immune activation is increasingly recognized as an important pathogenic component in antiphospholipid syndrome (APS). However, the clinical relevance of circulating cytokine alterations and their integrative immune patterns in APS remain incompletely understood.

Serum samples were obtained from 250 patients with APS and 81 healthy controls (HCs). Concentrations of 12 cytokines were measured using a multiplex bead-based immunoassay. Principal component analysis followed by K-means clustering was applied to identify cytokine-based subgroups among APS patients. Clinical manifestations and laboratory parameters were compared among clusters.

Compared with HCs, patients with APS showed significantly elevated levels of IL-6, IL-8, IL-12p70, and IFN-γ, together with reduced levels of IL-5 and TNF-α (all P < 0.05). Unsupervised clustering based on cytokine profiles identified four distinct immune phenotypes among APS patients, characterized by low-inflammatory, pan-inflammatory, selectively enriched inflammatory (TNF-α/IL-5-abundant), and T-cell-priming (IL-12p70, IL-2, and IL-4). In particular, the pan-inflammatory cluster was associated with higher adjusted Global Antiphospholipid Syndrome Score (aGAPSS), greater anticardiolipin antibody positivity, and more pronounced hematologic abnormalities, whereas the T-cell-priming cluster was abundant for primary APS and exhibited relatively lower systemic inflammatory burden.

APS is characterized by heterogeneous cytokine profiles reflecting distinct immune activation patterns. Cytokine-based clustering identifies clinically relevant inflammatory subgroups, supporting the potential value of immune stratification for improved risk assessment in APS. Key Points • Patients with APS exhibit a distinct circulating cytokine signature characterized by elevated IL-6, IL-8, IL-12p70, and IFN-γ with reduced IL-5 and TNF-α, underscoring the thrombo-inflammatory nature of the disease. • Unsupervised clustering of cytokine profiles identifies four immunologically distinct APS subgroups (low-inflammatory, pan-inflammatory, TNF-α/IL-5-abundant, and T-cell-priming), each associated with different clinical and laboratory features. • The pan-inflammatory cluster is linked to higher antiphospholipid antibody burden and greater hematologic abnormalities, whereas the T-cell-priming cluster is enriched for primary APS and exhibits a lower systemic inflammatory burden.