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Identification of a novel staining pattern of bile duct epithelial cells in primary sclerosing cholangitis.

Journal article
Authors Ardesjö
Portela-Gomes
Rorsman
Grimelius
Olov Ekwall
Published in Inflammatory bowel diseases
Volume 16
Issue 2
Pages 305-311
ISSN 1536-4844
Publication year 2010
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Pages 305-311
Language en
Links dx.doi.org/10.1002/ibd.21050
Keywords PDZK1; Primary sclerosing cholangitis; autoantigens; bile duct; epithelial cells
Subject categories Clinical immunology, Gastroenterology and Hepatology

Abstract

BACKGROUND:: Primary sclerosing cholangitis (PSC) is an inflammatory disease of the bile ducts with an unknown etiology. A number of autoantigens have been proposed, but an early diagnostic marker is still lacking. Our aim was to identify such an autoantigen. METHODS:: Immunostaining was performed on normal human bile duct with sera from patients with PSC and controls. To identify an autoantigen a cDNA library from normal human choledochus was constructed and immunoscreened with patient sera. Using in vitro transcription and translation and immunoprecipitation we examined the immunoreactivity against PDZ domain containing 1 (PDZK1) in 35 patients with PSC, 198 control patients, and 94 healthy controls. RESULTS:: We observed a previously unpublished staining pattern in which cytoplasmatic granules and apical cell membranes of biliary epithelial cells were stained by PSC sera. Strong immunoreactivity to these structures was obtained with 12 out of 35 PSC sera (34%) but not with sera from healthy controls. By screening the cDNA library we identified PDZK1 as a candidate antigen. Immunoreactivity against PDZK1 was detected in 9% of PSC patients, 2% of inflammatory bowel disease (IBD) patients, 8% of autoimmune pancreatitis patients, 18% of Grave's disease patients, and 1% of healthy controls. CONCLUSIONS:: Previously unpublished, specific, and strong autoantibodies against epithelial cells of the bile duct in PSC sera were identified. Furthermore, PDZK1 is suggested as a potential new autoantigen. Inflamm Bowel Dis 2009.

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