title: A global proteomic study identifies distinct pathological features of IgG4-related and primary sclerosing cholangitis.
abstract: OBJECTIVE
  This combined proteomic and histopathological study was aimed to compare tissue characteristics of immunoglobulin (Ig)G4-related sclerosing cholangitis (ISC) and primary sclerosing cholangitis (PSC) in a global, non-biased manner.
  
  
  RESULTS
  Tissue proteomes and phosphorylomes of frozen large bile duct samples were analysed by a conventional liquid chromatography-tandem mass spectrometry (LC-MS/MS) protocol and additional phosphopeptide enrichment methods. The proteomic examination identified 23 373 peptides and 4870 proteins, including 4801 phosphopeptides and 1121 phosphoproteins. The expression profiles of phosphopeptides discriminated ISC from PSC more clearly than those of non-phosphopeptides. In the pathway analysis, ISC was found to have 11 more activated signal cascades, including three immunological pathways, all B cell- or immunoglobulin-related. On immunostaining, two immunological markers (FYN-binding protein and allograft inflammatory factor-1) up-regulated in ISC were expressed mainly in M2 macrophages, consistent with increased phagocytotic activity induced by the immunoglobulin (Ig)G-Fcγ receptor interaction. In contrast, PSC had two more activated signal pathways related to extracellular matrix (ECM) remodelling. Filamin-A involved in ECM remodelling was expressed aberrantly in injured bile ducts and associated cholangiocarcinomas in PSC, suggesting its possible roles in periductal fibrosis and carcinogenesis in PSC.
  
  
  CONCLUSIONS
  This study suggested crucial roles of B cells and macrophages in ISC, and more dynamic ECM remodelling in PSC.
authors: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.|Institute of Liver Studies, King's College Hospital, London, UK.
authors: Yoh
authors: Y
authors: Zen
authors: Proteome Sciences plc, Cobham, UK.
authors: David
authors: D
authors: Britton
authors: Proteome Sciences plc, Cobham, UK.
authors: Vikram
authors: V
authors: Mitra
authors: Proteome Sciences plc, Cobham, UK.
authors: Ian
authors: I
authors: Pike
authors: Institute of Liver Studies, King's College Hospital, London, UK.
authors: Nigel
authors: N
authors: Heaton
authors: Institute of Liver Studies, King's College Hospital, London, UK.
authors: Alberto
authors: A
authors: Quaglia
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015209:Cholangitis, Sclerosing / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D016000:Cluster Analysis; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G; D020543:Proteome
keywords: B cell; autoimmune pancreatitis; pathogenesis; phosphoproteome; proteome