title: Association Between HLA Haplotypes and Increased Serum Levels of IgG4 in Patients With Primary Sclerosing Cholangitis.
abstract: Increased serum levels of IgG4 have been reported in 9%-15% of patients with primary sclerosing cholangitis (PSC); it is not clear whether this increase contributes to pathogenesis. We performed genetic analyses of the HLA complex in patients with PSC from Norway, Sweden, and from the United States. We found an association between levels of IgG4 above the upper reference limit and specific HLA haplotypes. These patients had a significantly lower frequency of the strongest PSC risk factor, HLA-B*08, than patients without increased IgG4, and significantly higher frequencies of HLA-B*07 and HLA-DRB1*15. HLA genotype therefore might affect the serum concentration of IgG4, and increased IgG4 might be a marker of a distinct phenotype of PSC.
authors: Norwegian Primary Sclerosing Cholangitis Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; KG Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
authors: Natalie L
authors: NL
authors: Berntsen
authors: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Olav
authors: O
authors: Klingenberg
authors: Division of Gastroenterology and Hepatology, Center for Basic Research in Digestive Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors: Brian D
authors: BD
authors: Juran
authors: Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors: Maria
authors: M
authors: Benito de Valle
authors: Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors: Björn
authors: B
authors: Lindkvist
authors: Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors: Konstantinos N
authors: KN
authors: Lazaridis
authors: Norwegian Primary Sclerosing Cholangitis Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Kirsten Muri
authors: KM
authors: Boberg
authors: Norwegian Primary Sclerosing Cholangitis Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; KG Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Tom H
authors: TH
authors: Karlsen
authors: Norwegian Primary Sclerosing Cholangitis Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; KG Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway. Electronic address: j.e.r.hov@medisin.uio.no.
authors: Johannes Roksund
authors: JR
authors: Hov
mesh_terms: D015415:Biomarkers / Q000097:blood; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D015793:HLA-B7 Antigen / Q000235:genetics; D015795:HLA-B8 Antigen / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D009664:Norway; D010641:Phenotype; D013548:Sweden; D014481:United States; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D015793:HLA-B7 Antigen; D015795:HLA-B8 Antigen; D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; D007074:Immunoglobulin G
keywords: Genetic Association Study; IgG4-Associated Cholangitis; Immune Response; Immunogenetics
references: Dig Liver Dis. 2014 Oct;46(10):903-8
references: 25091876
references: Gastroenterology. 2002 May;122(5):1264-9
references: 11984513
references: Hepatology. 1991 Jan;13(1):129-33
references: 1988334
references: Immunol Rev. 1999 Feb;167:257-74
references: 10319267
references: Tissue Antigens. 1999 May;53(5):459-69
references: 10372541
references: Am J Gastroenterol. 2006 Sep;101(9):2070-5
references: 16879434
references: Tissue Antigens. 2007 Feb;69(2):161-9
references: 17257319
references: Gastroenterology. 2008 Mar;134(3):706-15
references: 18222442
references: J Hepatol. 2010 May;52(5):712-7
references: 20347497
references: J Hepatobiliary Pancreat Sci. 2012 Sep;19(5):536-42
references: 22717980
references: Nat Genet. 2013 Jun;45(6):670-5
references: 23603763
references: Hepatology. 2013 Jun;57(6):2390-8
references: 23300096
references: Lancet. 2013 Nov 9;382(9904):1587-99
references: 23810223
references: Hepatology. 2014 May;59(5):1954-63
references: 24375491