The involvement of autoimmunity in PSC has been further strengthened by recent data demonstrating that ANCAs to serine proteinase-3 (PR3-ANCAs) detected by bead-based immunoassays can occur in PSC and even have a predictive value for severe disease and the occurrence of cholangiocarcinoma (CCA) [11,12,13]. This evidence concerns the gene PRTN3 and cholangiocarcinoma.