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Biochemical and immuno-pathological aspects of tissue transglutaminase in coeliac disease

Roth, Bodil LU ; Sjöberg, Klas LU and Stenberg, P (2003) In Autoimmunity 36(4). p.221-226
Abstract
Tissue transglutaminase (tTg) has been identified as the major autoantigen in coeliac disease (CD). ELISA methods have been developed for measuring the autoantibody. There are divergent reports on the effects of calcium on the antibody binding to tTg. Furthermore, zinc is a potent inhibitor of tTg. To better understand the role of transglutaminase in CD, we have studied the stability of commercial tTG, the effect of CD serum on tTg-activity and the effects of calcium and zinc on the antibody binding. The inclusion of calcium during the coating of the ELISA plates significantly increases the binding of the antibody, while zinc at physiological concentrations inhibits the binding. Moreover, our results show that commercial guinea pig liver... (More)
Tissue transglutaminase (tTg) has been identified as the major autoantigen in coeliac disease (CD). ELISA methods have been developed for measuring the autoantibody. There are divergent reports on the effects of calcium on the antibody binding to tTg. Furthermore, zinc is a potent inhibitor of tTg. To better understand the role of transglutaminase in CD, we have studied the stability of commercial tTG, the effect of CD serum on tTg-activity and the effects of calcium and zinc on the antibody binding. The inclusion of calcium during the coating of the ELISA plates significantly increases the binding of the antibody, while zinc at physiological concentrations inhibits the binding. Moreover, our results show that commercial guinea pig liver Tg treated with calcium contains at least four major antigenic molecules and is a labile enzyme, which is degraded rapidly by contaminating proteases. Human serum contains anti-proteases that protect the enzyme. Probably, the labile character of commercial tTG explains the divergent reports on the effects of calcium on antibody binding. Finally, antibodies in serum from a CD patient do not seem to inhibit tTg activity. Hypothetically, low, intestinal Zn2+ -levels facilitate Ca2+ -activation of tTg, which deamidates gliadin. A complex between tTg and modified gliadin forms the antigen and triggers the immune reaction leading to manifest CD. Hypozincaemia secondary to villous atrophy aggravates the induced disease. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
thioester, calcium, zinc, coeliac, transglutaminase, activity staining
in
Autoimmunity
volume
36
issue
4
pages
221 - 226
publisher
Taylor & Francis
external identifiers
  • wos:000184432600005
  • pmid:14563015
  • scopus:0042093621
ISSN
0891-6934
DOI
10.1080/0891693031000118974
language
English
LU publication?
yes
id
5e9de4b0-db3d-460e-9533-d6d73e5f72fd (old id 305113)
date added to LUP
2007-09-20 18:51:04
date last changed
2018-05-29 10:53:25
@article{5e9de4b0-db3d-460e-9533-d6d73e5f72fd,
  abstract     = {Tissue transglutaminase (tTg) has been identified as the major autoantigen in coeliac disease (CD). ELISA methods have been developed for measuring the autoantibody. There are divergent reports on the effects of calcium on the antibody binding to tTg. Furthermore, zinc is a potent inhibitor of tTg. To better understand the role of transglutaminase in CD, we have studied the stability of commercial tTG, the effect of CD serum on tTg-activity and the effects of calcium and zinc on the antibody binding. The inclusion of calcium during the coating of the ELISA plates significantly increases the binding of the antibody, while zinc at physiological concentrations inhibits the binding. Moreover, our results show that commercial guinea pig liver Tg treated with calcium contains at least four major antigenic molecules and is a labile enzyme, which is degraded rapidly by contaminating proteases. Human serum contains anti-proteases that protect the enzyme. Probably, the labile character of commercial tTG explains the divergent reports on the effects of calcium on antibody binding. Finally, antibodies in serum from a CD patient do not seem to inhibit tTg activity. Hypothetically, low, intestinal Zn2+ -levels facilitate Ca2+ -activation of tTg, which deamidates gliadin. A complex between tTg and modified gliadin forms the antigen and triggers the immune reaction leading to manifest CD. Hypozincaemia secondary to villous atrophy aggravates the induced disease.},
  author       = {Roth, Bodil and Sjöberg, Klas and Stenberg, P},
  issn         = {0891-6934},
  keyword      = {thioester,calcium,zinc,coeliac,transglutaminase,activity staining},
  language     = {eng},
  number       = {4},
  pages        = {221--226},
  publisher    = {Taylor & Francis},
  series       = {Autoimmunity},
  title        = {Biochemical and immuno-pathological aspects of tissue transglutaminase in coeliac disease},
  url          = {http://dx.doi.org/10.1080/0891693031000118974},
  volume       = {36},
  year         = {2003},
}