In conclusion, although it is already widely known that HMGB1 can induce and improve innate immunity, playing a role in the inflammatory phenomena of autoimmune diseases, our findings suggest that, in subjects with APS, not only elevated levels of HMGB1 but also of sRAGE may represent an alarm signal, indicating an increase of proinflammatory triggers. Here, HMGB1 is linked to autoimmune disease.