Coeliac disease autoantibodies mediate significant inhibition of tissue transglutaminase.
The detection of antibodies directed against tissue transglutaminase (tTG) in serum is a sensitive and specific test for suspected coeliac disease. tTG is a ubiquitous, multifunctional enzyme that has been implicated in many important physiological processes as well as the site-specific deamidation of glutamine residues in gluten-derived peptides. This modification of gluten peptides facilitates their binding to HLA-DQ2, which results in amplification of the T-cell response to gluten. The purpose of this study was to investigate the possibility that patient IgA autoantibodies directed against tTG interfere with the crosslinking activity of the enzyme. IgA autoantibodies against tTG were isolated/depleted from patient serum and tested for their capacity to interfere with tTG activity in vitro using a sensitive fluorescence-based activity assay. We have demonstrated that autoantibodies cause significant inhibition of tTG-mediated crosslinking at equimolar and 2:1 ratios of antibody to enzyme.
Byrne
Greg
G
National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland. greg.byrne@ucd.ie
Feighery
Con
C
Jackson
John
J
Kelly
Jacinta
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D002446:Celiac Disease / Q000201:enzymology* / Q000276:immunology*; D005260:Female; D019204:GTP-Binding Proteins; D005983:Glutens / Q000276:immunology / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
D001323:Autoantibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D007070:Immunoglobulin A; D011994:Recombinant Proteins; D005983:Glutens; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins