Type I cryoglobulinemia (monoclonal Igs, typically IgG or IgM rarely IgA or free light chain) develops in the setting of lymphoproliferative or hematologic disorders of B cell lineage; type II mixed cryoglobulinemia [monoclonal IgM (or IgG or IgA) with rheumatoid factor activity and polyclonal Ig] develops in infections, autoimmune diseases and lymphoproliferative disorders; type III cryoglobulinemia (polyclonal IgG (all isotypes) and polyclonal IgM) is associated with autoimmune disorders and infections [65,66]. This evidence concerns the gene CUBN and autoimmune disease.