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Investigation of goblet cell autoantigens in patients with inflammatory bowel disease.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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(English)Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-97135OAI: oai:DiVA.org:uu-97135DiVA: diva2:171939
Available from: 2008-04-24 Created: 2008-04-24 Last updated: 2010-05-07Bibliographically approved
In thesis
1. Autoantigens in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis
Open this publication in new window or tab >>Autoantigens in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Inflammatory bowel disease (IBD) comprises diseases that are characterized by chronic or relapsing inflammation of the gastrointestinal tract. Primary sclerosing cholangitis (PSC) is an extraintestinal manifestation in IBD. Immunoreactivity against an autoantigen that is expressed both in the gastrointestinal tract and the biliary tract could be the link between these diseases. A possible source of such an antigen is goblet cells.

Immunostainings of normal human tissues using IBD patient sera showed goblet cell immunoreactivity against goblet cells in all parts of the gastrointestinal tract. The most frequent immunostaining was found against goblet cells in the appendix against which 84% (42/50) of IBD patients compared to 8% (4/50) of healthy blood donors showed immunoreactivity. To identify the corresponding antigen we used three different approaches, investigation of immunoreactivity to different candidate proteins compared to IBD sera, immunoscreening of an appendiceal cDNA library, and immunoprecipitation of protein lysates from mucin producing cells followed by SDS-PAGE and 2D gel electrophoresis. These approaches led to the identification of several candidate autoantigens of which complement C3 is the most promising.

A novel staining pattern with strong immunoreactivity to granules and the apical membrane of biliary epithelial cells was identified with 35% (12/34) of PSC sera compared to none of healthy controls (n=28). Screening of a cDNA library from normal human choledochus identified PDZ domain containing 1 (Pdzk1) and Glutathion S transferase theta 1 (GSTT1) as potential candidates. Pdzk1 is an interesting candidate which is expressed in the intestinal tract and bile ducts. GSTT1 antibodies were not specific for PSC and are thought to develop as an alloimmune response in patients with the GSTT1-null genotype.

In conclusion, we have identified specific immunoreactivity to goblet cells and biliary epithelial cells using sera from patients with IBD and PSC respectively. We have also identified several potential autoantigens.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 62 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 342
Keyword
Molecular medicine, inflammatory bowel disease, primary sclerosing cholangitis, autoimmunity, autoantigen, goblet cell, Molekylärmedicin
Identifiers
urn:nbn:se:uu:diva-8677 (URN)978-91-554-7180-4 (ISBN)
Public defence
2008-05-15, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:15 (English)
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Available from: 2008-04-24 Created: 2008-04-24 Last updated: 2010-05-07Bibliographically approved

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