Celiaki som modell för autoimmun sjukdom. Transglutaminas har nyckelroll--stressreaktion sätter fart på ond cirkel

The autoantigen of endomysial antibodies in coeliac disease has been found to be an enzyme, tissue transglutaminase. Zinc inhibits the calcium-dependent activation of this thiol enzyme and also decreases the affinity between transglutaminase and the antibodies. Physiologically, transglutaminases catalyse the formation of bridges between lysine- and glutamine-containing peptides. Theoretically, if accidentally activated, for example due to a stress-induced low concentration of intestinal zinc, tissue transglutaminase will sequentially deamidate specific glutamine residues in gliadins. During this process, an abnormally long-lived thioester intermediate between the active site cysteine of the enzyme and a previously, partly deamidated gliadine may trigger the T-cells in persons with HLA DQ2/DQ8, generating antibodies against both transglutaminase and gliadin. Furthermore, the resulting villous atrophy decreases the absorption of zinc, thus causing a vicious circle. In rheumatoid arthritis a similar pattern is observed with the formation of antibodies against citrulline as well as against the calcium-dependent citrullinating thiol-enzyme, peptidylargininedeiminase, which also is inhibited by zinc.