Tissue transglutaminase and combined screening for coeliac disease and type 1 diabetesassociated autoantibodies

Abstract

Detection of anti-gliadin antibodies and autoantibodes to endomysium (EMA) in apparently healthy people identifies silent coeliac disease, which, if treated by a gluten-free diet virtually eliminates the risk of complications associated with untreated disease. 1 Maki M Collin P Coeliac disease. Lancet. 1997; 349: 1755-1759 Summary Full Text Full Text PDF PubMed Scopus (563) Google Scholar EMA, which are detected by fairly cumbersome indirect immunofluorescence assays, are the more sensitive and specific marker for screening. 2 Catassi C Ratsch I-M Fabiani E et al. Coeliac disease in the year 2000: exploring the iceberg. Lancet. 1994; 343: 200-203 Summary PubMed Scopus (616) Google Scholar The autoantigen specificity of EMA has been identified as tissue transglutaminase C, 3 Dieterich W Ehnis T Bauer M et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med. 1997; 3: 797-801 Crossref PubMed Scopus (1771) Google Scholar making it possible to develop high- throughput antigen-specific assays. For this purpose the human tissue transglutaminase C cDNA was cloned and translated, in vitro, and a protein-A-based radio-binding assay developed for tissue transglutaminase autoantibody detection. This assay detected antibodies in 109 (98%) of 111 untreated patients with coeliac disease, including nine previously identified through screening with EMA and two with IgA deficiency; and in three of 92 age-matched controls. An IgA ELISA with guinea-pig liver tissue transglutaminase C (Sigma) detected antibodies in 94 (84%) patients and in seven (8%) controls, and the IgA-EMA test found antibodies in 108 patients and one control. One of the controls had raised antibody binding in all assays.