Identification of common epitopes on gliadin, enterocytes, and calreticulin recognised by antigliadin antibodies of patients with coeliac disease

Background-Sera of patients with coeliac disease, containing IgA and IgG an tigliadin antibodies (AGA) and various IgA autoantibodies, react with isola ted enterocytes. AGA cross react with enterocyte antigens, one of which has been identified as calreticulin. Aims-To characterise the antigenic structures of gliadin, enterocytes, and calreticulin recognised by AGA from patients with active coeliac disease. Methods-AGA were isolated from sera of nine patients by affinity chromatogr aphy and tested by competitive ELISA using 40 a-gliadin synthetic dodecapep tides (A1-F6). Results-Reactivity of gliadin with all purified AGA tested was inhibited by peptide A4 at the N-terminal region; by C2, C3, and D4 at the central regi on; and by F3 and F4 at the C-terminal region of the gliadin molecule. AGA cross reactivity with enterocytes was inhibited by peptides A4, D1-D4, and F6 and with calreticulin by peptides A4, D3, and D4. As dominant epitopes A GA of coeliac patients recognise similar structures corresponding to peptid es A4, D3, D4, and F6 present on gliadin, enterocytes, and calreticulin. Su bstitution of glutamine in the A4 peptide by glutamic acid caused loss of i nhibitory capacity. Shortening of peptide A4 on the N-terminal by three ami no acids increased its inhibitory effect. Conclusions-AGA of patients with coeliac disease react with similar structu res on gliadin and potential autoantigens on enterocytes.