title: Immunoglobulin G4(+) B-cell receptor clones distinguish immunoglobulin G 4-related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies.
abstract: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) of the biliary tree and pancreas is difficult to distinguish from sclerosing cholangitis and biliary/pancreatic malignancies (CA). An accurate noninvasive test for diagnosis and monitoring of disease activity is lacking. We demonstrate that dominant IgG4(+) B-cell receptor (BCR) clones determined by next-generation sequencing accurately distinguish patients with IgG4-associated cholangitis/autoimmune pancreatitis (n = 34) from those with primary sclerosing cholangitis (n = 17) and CA (n = 17). A novel, more affordable, and widely applicable quantitative polymerase chain reaction (qPCR) protocol analyzing the IgG4/IgG RNA ratio in blood also achieves excellent diagnostic accuracy (n = 125). Moreover, this qPCR test performed better than serum IgG4 levels in sensitivity (94% vs. 86%) and specificity (99% vs. 73%) and correlates with treatment response (n = 20).
  
  
  
  IgG4(+) BCR clones and IgG4/IgG RNA ratio markedly improve delineation, early diagnosis, and monitoring of IgG4-RD of the biliary tree and pancreas. (Hepatology 2016;64:501-507).
authors.affiliation: Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology & Rheumatology, Academic Medical Center, Amsterdam, The Netherlands.|Department of Genome Analysis, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marieke E
authors.initials: ME
authors.lastname: Doorenspleet
authors.affiliation: Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Lowiek M
authors.initials: LM
authors.lastname: Hubers
authors.affiliation: Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom.|NDM Oxford University, Oxford Martin School, Oxford University, Oxford, United Kingdom.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Culver
authors.affiliation: Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Lucas J
authors.initials: LJ
authors.lastname: Maillette de Buy Wenniger
authors.affiliation: Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology & Rheumatology, Academic Medical Center, Amsterdam, The Netherlands.|Department of Genome Analysis, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Klarenbeek
authors.affiliation: Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom.|NDM Oxford University, Oxford Martin School, Oxford University, Oxford, United Kingdom.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Chapman
authors.affiliation: Department of Genome Analysis, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.affiliation: Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Stan F
authors.initials: SF
authors.lastname: van de Graaf
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Joanne
authors.initials: J
authors.lastname: Verheij
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Gulik
authors.affiliation: Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom.|NDM Oxford University, Oxford Martin School, Oxford University, Oxford, United Kingdom.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Barnes
authors.affiliation: Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.affiliation: Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology & Rheumatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Niek
authors.initials: N
authors.lastname: de Vries
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001649:Bile Duct Diseases / Q000175:diagnosis* / Q000276:immunology; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D007074:Immunoglobulin G