Genetic Distinctions in Patients With Primary Sclerosing Cholangitis: Immunoglobulin G4 Elevations and HLA Risk  Evaggelia Liaskou, Gideon M. Hirschfield  Gastroenterology  Volume 148, Issue 5, Pages 886-889 (May 2015) DOI: 10.1053/j.gastro.2015.03.021 Copyright © 2015 AGA Institute Terms and Conditions

Figure 1 Dissecting the pathogenesis of primary sclerosing cholangitis (PSC). PSC is characterized by an overwhelming association with the major histocompatibility complex (MHC), which is also known in humans as the human leukocyte antigen (HLA). A strong association with HLA-B*08, HLA-DRB1*03:01 and HLA-DRB1*15:01 alleles in PSC has been reported. However, the triggering (auto)antigen/s in PSC are unknown as is their route of entry. The role played by HLA-DR molecules in exogenous antigen presentation to CD4+ T-helper cells may help to explain their association with PSC disease. Exogenous peripheral antigens entering the liver are internalized via antigen-presenting cells (APC), degraded and preferentially bound by HLA class II molecules; the HLA class II–peptide complex is then transported to the cell surface for recognition by CD4+ T-helper T cells bearing the antigen-specific T-cell receptor (TCR). The adaptive immune response also selectively expands B cells; activated B cells differentiate into plasma cells producing immunoglobulins (IgG4, IgA, IgM, IgG) able to bind to the cognate antigen that caused the activation of the precursor B cell. (PSC HLA distinctions are based on previous reports). Gastroenterology 2015 148, 886-889DOI: (10.1053/j.gastro.2015.03.021) Copyright © 2015 AGA Institute Terms and Conditions