title: Antineutrophil antibodies define clinical and genetic subgroups in primary sclerosing cholangitis.
abstract: The strongest genetic risk factors in primary sclerosing cholangitis (PSC) are encoded in the HLA complex. Antineutrophil cytoplasmic antibodies (ANCA) have been reported in up to 94% of PSC patients, but their clinical significance and immunogenetic basis are ill defined. We aimed to characterize clinical and genetic associations of ANCA in PSC.
  
  
  
  Antineutrophil cytoplasmic antibodies were analysed with indirect immunofluorescence in 241 Norwegian PSC patients. HLA-B and HLA-DRB1 genotyping was performed in the patients and in 368 healthy controls. Data on perinuclear ANCA (pANCA) and HLA-DRB1 were available from 274 ulcerative colitis (UC) patients without known liver disease.
  
  
  
  Antineutrophil cytoplasmic antibodies were found in 193 (80%) of the PSC patients, with pANCA in 169 (70%). ANCA-positive patients were younger than ANCA negative at diagnosis of PSC and had a lower frequency of biliary cancer (9% vs 19%, P=.047). There were no differences between PSC patients with and without inflammatory bowel disease. Genetically, the strong PSC risk factors HLA-B*08 (frequency in healthy 13%) and DRB1*03 (14%) were more prevalent in ANCA-positive than -negative patients (43% vs 25%, P=.0012 and 43% vs 25%, P=.0015 respectively). The results were similar when restricting the analysis to pANCA-positive patients. In UC patients without liver disease, HLA-DRB1*03 was more prevalent in pANCA-positive compared with -negative patients (P=.03).
  
  
  
  Antineutrophil cytoplasmic antibodies identified PSC patients with particular clinical and genetic characteristics, suggesting that ANCA may mark a clinically relevant pathogenetic subgroup in the PSC-UC disease spectrum.
authors: Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Section of Gastroenterology, Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Division of Surgery, Inflammatory Medicine and Transplantation, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.|K.G.Jebsen Inflammation Research Centre, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors: Johannes R
authors: 0000-0002-5900-8096
authors: JR
authors: Hov
authors: Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Section of Gastroenterology, Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Kirsten M
authors: KM
authors: Boberg
authors: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|K.G.Jebsen Inflammation Research Centre, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Eli
authors: E
authors: Taraldsrud
authors: Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.|National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.
authors: Mette
authors: M
authors: Vesterhus
authors: Clinical Center of Endocrinology, Medical University Sofia, Sofia, Bulgaria.
authors: Maria
authors: M
authors: Boyadzhieva
authors: Division of Medicine, Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway.
authors: Inger Camilla
authors: IC
authors: Solberg
authors: Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors: Erik
authors: E
authors: Schrumpf
authors: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|EpiGen Institute, Campus AHUS, Akershus University Hospital, Nordbyhagen, Norway.
authors: Morten H
authors: MH
authors: Vatn
authors: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|K.G.Jebsen Inflammation Research Centre, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Benedicte A
authors: BA
authors: Lie
authors: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Rheumatology Unit, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Øyvind
authors: Ø
authors: Molberg
authors: Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Section of Gastroenterology, Division of Surgery, Department of Transplantation Medicine, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Division of Surgery, Inflammatory Medicine and Transplantation, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.|K.G.Jebsen Inflammation Research Centre, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors: Tom H
authors: TH
authors: Karlsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D015415:Biomarkers; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000097:blood* / Q000235:genetics*; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005838:Genotype; D015796:HLA-B27 Antigen / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009664:Norway; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; C090660:HLA-B protein, human; D015796:HLA-B27 Antigen; D059811:HLA-DRB1 Chains
keywords: 
  HLA
  ; antineutrophil cytoplasmic antibodies; primary sclerosing cholangitis