HLA-DRB1 and immunoglobulin G4-related sclerosing disease: Genetic factors: Like in other immune-mediated diseases including fibrosing cholangiopathies such as PBC or PSC, several HLA and non-HLA gene variants have been identified as risk genes for various manifestations of IgG4-RD, but not specifically IRC in association studies as summarized by Ishikawa and Terao.52Among these, HLA-DRB1 was identified as a risk gene in a Japanese genome-wide association study53suggesting that antigen presentation and recognition may play a critical role in the pathogenesis of IgG4-RD.