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

Background&aims The strongest genetic risk factors in primary sclerosing cholangitis (PSC) are encoded in the HLA complex. Anti-neutrophil 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 ANCA were analyzed 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 ANCA 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=0.047). There were no differences between PSC patients with and without IBD. 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=0.0012 and 43% vs 25%, P=0.0015, 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 cases (P=0.03). Conclusions ANCA 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. This article is protected by copyright. All rights reserved.