Ricerc@Sapienza

Mixed cryoglobulinemia (MC) is a systemic leukocytoclastic vasculitis involving small and medium-sized vessels and characterized by the deposition of cold-precipitable IgG-IgM immune complexes, called cryoglobulins. The main cause of MC is chronic hepatitis C virus (HCV) infection, representing 70-90% MC. Of note, conversely, the presence of circulating cryoglobulins is identified in about 50% of HCV-infected patients, although only 5-10% of them have a symptomatic cryoglobulinemic vasculitis. The contribution of endothelial damage and/or coagulation dysfunction to the clinical manifestations of MC, either HCV-associated or essential, has been poorly investigated so far. Our project aims to analyze the possible influence of haemostatic dysfunction in vasculitis development and to find biomarkers able to predict those patients with HCV-associated MC and circulating cryoglobulins at risk for vasculitis development.
In vivo platelet activation (through the measurement of sCD40L and sP-selectin) and markers of endothelial activation, namely PAI-1 and vWF, have been found to be elevated in patients with HCV infection but a possible influence of cryoglobulins in the endothelial damage has not been investigated. Because of the strict correlation of the coagulation cascade and the inflammatory network we will analyze markers of coagulation activation in vivo and bio-humoral markers of inflammation as TNF-alpha and IL-6, C-reactive protein and VCAM-1. This latter molecule has been already found increased in severe forms of HCV-associated MC but never investigated in essential MC.
The results of our project may provide simple and measurable factors that indicate endothelial and/or coagulation system dysfunction possibly able to stratify HCV-infected patients at risk for vasculits and able to shed light in the pathogenesis of leukocytoclastic vasculitis in MC, defining disease-specific haemostatic characteristics in essential or HCV-associated MC.