Biochemical and immuno-pathological aspects of tissue transglutaminase in coeliac disease.
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.
Roth
E Bodil
EB
Hospital Pharmacy, Malmö University Hospital, S-205 02 Malmö, Sweden.
Sjöberg
Klas
K
Stenberg
Pål
P
D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D002446:Celiac Disease / Q000201:enzymology* / Q000276:immunology; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005903:Gliadin / Q000276:immunology / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008875:Middle Aged; D011503:Transglutaminases / Q000276:immunology* / Q000378:metabolism; D015032:Zinc / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D001324:Autoantigens; D005903:Gliadin; D011503:Transglutaminases; D015032:Zinc; D002118:Calcium