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. 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 ‐ DRB 1 genotyping was performed in the patients and in 368 healthy controls. Data on perinuclear ANCA ( pANCA ) and HLA ‐ DRB 1 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 DRB 1*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 ‐ DRB 1*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.