Antibody response to dietary and autoantigens in Gαi2-deficient mice

Holm H. Uhlig, Elisabeth Hultgren Hörnquist, Lena Öhman Bache, Uwe Rudolph, Lutz Birnbaumer, Thomas Mothes

Research output: Contribution to journalArticle

Abstract

Background: Mice with a targeted mutation in the G protein subunit Gαi2 gene develop a colonic mucosal inflammation, with a highly activated B-cell response. We wanted to investigate whether this increased B-cell activity was directed against dietary antigens and/or various self tissues. Methods: The level of antibodies specific for dietary (gliadin, soya and fish meal) antigens was measured by ELISA. Reactivity against self antigens was measured by immunohistochemistry on cryo-sectioned mouse and rat tissue. Sera and intestinal lavages were analysed from Gαi2-/- mice before and after development of colitis and in age-matched wild type litter mates. Results: Titres of antibodies against dietary antigens were significantly enhanced both in serum and in large intestinal lavages from Gαi2-/- mice with ongoing colitis but not prior to disease, as compared to wild type mice. The autoreactivity to self tissues was significantly increased in Gαi2-/- mice both before and after development of colitis as compared to litter mate control animals. Self tissue reactivity was directed not only against epithelial cells of the colon, small intestine and gastric glands, but also against smooth muscle cells, hepatocytes, bile duct cells, renal tubule and collecting tubule cells of the kidney. In analogy to human ulcerative colitis, autoantibodies against epithelial cells, bile duct epithelium and neutrophil granulocytes were found. Conclusions: Earlier increase in levels of autoantibodies (before onset of colitis) than of food antibodies (after onset of colitis) suggests the latter response to be a secondary phenomenon to e.g. a destroyed barrier function.

Original languageEnglish (US)
Pages (from-to)1421-1429
Number of pages9
JournalEuropean Journal of Gastroenterology and Hepatology
Volume13
Issue number12
DOIs
StatePublished - Dec 31 2001
Externally publishedYes

Keywords

  • Autoantibodies
  • Autoimmunity
  • Dietary antibodies
  • Gαi2 deficiency
  • Inflammatory bowel disease
  • Mice
  • Ulcerative colitis

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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