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Immunoreactivity against goblet cells in patients with inflammatory bowel disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Autoimmuna sjukdomar (Kämpe))
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (magtarm)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
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2008 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 14, no 5, 652-661 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A number of autoantibodies have been reported in inflammatory bowel disease (IBD). The aim of this study was to investigate to what extent sera from patients with IBD contain autoantibodies directed against normal human gastrointestinal mucosa. METHODS: Samples of sera from 50 patients with IBD and 50 healthy subjects were used for immunostaining of normal and affected human gastrointestinal tissues. RESULTS: Eighty-four percent of the sera from IBD patients showed immunoreactivity against goblet cells in the appendix compared with 8% of the sera from healthy subjects. Goblet cell reactivity of IBD patient sera varied between regions in the gastrointestinal tract. Sera from healthy subjects only reacted with goblet cells in the appendix. In the colon and the appendix, goblet cell reactivity of IBD sera was generally weak at the base of the crypts and gradually increased toward the lumen. Three IBD sera samples reacted with gastrin cells in the antrum. In colon biopsies from patients with ulcerative colitis, immunoreactivity against the remaining goblet cells showed an inverse correlation with inflammatory activity. CONCLUSIONS: These findings suggest that immunoreactivity against goblet cells may be of central importance in the pathogenesis of IBD. Identification of goblet cell antigens could lead to a better understanding of IBD and provide a new diagnostic tool.

Place, publisher, year, edition, pages
2008. Vol. 14, no 5, 652-661 p.
Keyword [en]
inflammatory bowel disease, goblet cells, autoimmunity, autoantibodies
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97134DOI: 10.1002/ibd.20370ISI: 000255581500009PubMedID: 18213698OAI: oai:DiVA.org:uu-97134DiVA: diva2:171938
Available from: 2008-04-24 Created: 2008-04-24 Last updated: 2011-05-12Bibliographically 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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Ardesjö, BritaKämpe, Olle

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Department of Medical SciencesDepartment of Genetics and PathologyDepartment of Women's and Children's HealthCentre for Clinical Research, County of Västmanland
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