Antineutrophil antibodies define clinical and genetic subgroups in primary sclerosing cholangitis.

Abstract

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.

• Authors: Johannes R Hov, Kirsten M Boberg, Eli Taraldsrud, Mette Vesterhus, Maria Boyadzhieva, Inger Camilla Solberg, Erik Schrumpf, Morten H Vatn, Benedicte A Lie, Øyvind Molberg, Tom H Karlsen
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 37 Issue 3 Pg. 458-465 (03 2017) ISSN: 1478-3231 [Electronic] United States
• PMID: 27558072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antibodies, Antineutrophil Cytoplasmic
• Biomarkers
• HLA-B protein, human
• HLA-B27 Antigen
• HLA-DRB1 Chains

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Antineutrophil Cytoplasmic (blood)
• Biomarkers
• Case-Control Studies
• Cholangitis, Sclerosing (blood, genetics)
• Cross-Sectional Studies
• Databases, Factual
• Female
• Fluorescent Antibody Technique, Indirect
• Genotype
• HLA-B27 Antigen (genetics)
• HLA-DRB1 Chains (genetics)
• Humans
• Inflammatory Bowel Diseases (genetics)
• Logistic Models
• Male
• Middle Aged
• Norway
• Young Adult