Relevance of inflammatory and complement activation biomarkers profiling in antiphospholipid syndrome patients outside acute thrombosis

Objective To evaluate whether inflammatory and complement biomarkers are associated with specific characteristics of antiphospholipid syndrome (APS). Methods Serum levels of interleukin ( IL)-1 beta (IL-1 beta), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, interferon-alpha (IFN)-alpha, IFN-gamma, vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule (VCAM)-1, and plasma levels of soluble C5b-9 (sC5b-9), C3a, C4a, Bb fragment were measured in unselected APS patients. Twenty-five healthy blood donors were included as controls. Results Between January 2020 and April 2021, 98 APS patients were included outside acute thrombosis (median time from the last APS manifestation: 60 (23;132) months). Levels of IL6, VCAM-1, sC5b-9, C3a, C4a, and Bb were significantly increased in APS patients compared to controls. A cluster analysis allowed to divide patients into two clusters: "inflammatory" (higher levels of IL-6 and VCAM-1) and "complement". In APS, elevated IL-6 was associated with hypertension, diabetes, BMI, and hypertriglyceridaemia. 85% of our APS patients had elevated levels of at least one complement biomarker. Elevated Bb (34%) was associated with aPL positivities, especially with triple aPL positivity (50% vs. 18%, p<0.001). 7/8 patients with history of catastrophic APS had elevated levels of complement biomarkers. Conclusion Our findings suggested that APS patients outside acute thrombosis might be divided into two clusters: "inflammatory" and "complement". Elevated IL-6 was associated with cardiovascular risk factors and metabolic parameters, whereas Bb fragments, a marker of alternative pathway complement activation, was strongly associated with aPL profile at highest risk of severe disease.