According to the definition of Brouet et al. [15], mixed cryoglobulinemias consist of monoclonal/polyclonal IgM with RF activity and according to Napodano et al. [26], 95% of CG consist of immune complexes with RF, however in reality, studies show a lower percentage of samples with RF activity since RF is in complex with polyclonal IgG and could only be detected with complex dissociation, which is not routinely used. This evidence concerns the gene CD40LG and cryoglobulinemia.