Antibodies to human recombinant tissue transglutaminase measured by radioligand assay: Evidence for high diagnostic sensitivity for celiac disease

Celiac disease is associated with endomysial antibodies (EmA), which have r ecently been reported to be directed to tissue transglutaminase (tTG). To d emonstrate binding of antibodies to recombinant tTG, human tTG was cloned, expressed by in vitro transcription/translation and used to develop novel r adioligand assays for combined and single detection of immunoglobulin A (Ig A) and G (IgG)-specific antibodies. IgA and IgG-tTGA were found in 43 (95.6 %) of 45 patients with newly-diagnosed celiac disease Verified by biopsy. I n addition, all 30 sera from patients with gastrointestinal symptoms and po sitive EmA were positive for IgA-tTGA, and all but one serum (96.7 %) had a ntibodies of the IgG class. Receiver-operating characteristic analysis incl uding 574 sera from healthy controls revealed a specificity of 99.5 %. By m eans of these new assays, we identified all patients with endomysial antibo dies and achieved, at equal specificity, an even improved sensitivity (95.6 %) as compared to EmA (91.1 %) detected by the standard immunofluorescence test. Here, we have provided direct evidence that recombinant tTG is a majo r target of antibodies in celiac disease. Our data suggest that tTGA measur ed by radioligand assay have the power to overcome the limitations of the E mA-test. This new strategy may considerably facilitate large-scale screenin g for silent and latent celiac disease.