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Lancet. 1984 Nov 3;2(8410):1009-13.

Aberrant expression of HLA-DR antigens on bileduct epithelium in primary biliary cirrhosis: relevance to pathogenesis.


Direct immunofluorescence with an avidinbiotin system was used to investigate the expression of MHC molecules HLA-DR and HLA-A,B,C on bileducts in cryostat sections from 10 primary biliary cirrhosis (PBC) patients. Needle biopsy specimens from 55 patients with various chronic liver disorders, surgical biopsy specimens from 2 patients with recurrent secondary cholangitis, and 4 normal livers were used as controls. Normal bileducts did not express DR whereas in 8/10 PBC biopsy specimens there were varying degrees of cytoplasmic DR staining in septal or interlobular bileduct epithelium. In the early histological stages of PBC the aberrant DR expression was multifocal, but in late-stage specimens whatever ducts remained were all positive. This pattern resembles that in focal thyroiditis and suggests that DR expression is an early manifestation of autoimmune cholangitis. In 6/61 control biopsies only weak staining was detected in occasional small interlobular ducts. The class I HLA-A,B,C expression normally seen on biliary epithelium was increased in 8/10 PBC cases and in 19/61 non-PBC biopsies. Perhaps the aberrant expression of HLA-DR antigens on bileduct epithelium in PBC enables these cells to present "self antigens" to sensitised T-lymphocytes and to promote autorecognition, possibly in response to several environmental triggers; the increased HLA-A,B,C, expression may be a means of amplifying T-cell cytotoxic responses.

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