IL-12A and IL-12RB2 variants confer an augmented risk of autoimmunity in many human conditions and have been recently validated in a meta-analysis of several PBC GWAS.17, 18, 19, 43, 44, 45, 46 The significance of this observation is elegantly illustrated in experimental cholangiopathy models, wherein mice that lack the p40 subunit of IL-12 (IL12p40−/−) exhibit dramatic reductions in histologic cholangitis and a significant decrease in the levels of intrahepatic, proinflammatory cytokines.47 This evidence concerns the gene IL12A and primary biliary cholangitis.