Tissue transglutaminase as the autoantigen of coeliac disease

Dieterich et al show that immunoprecipitation of human fibrosarcoma cell lysates (cell line HT1080) using the IgA fraction from serum samples of patients with coeliac disease results in a single protein band with a molecular weight of 85 kDa. Immunoprecipitation occurred exclusively with 25 coeliac disease serum samples, but with none of the 25 control samples. The 85 kDa antigen was cleaved with endoproteinase Asp-N, and after amino-terminal sequence analysis, the three cleavage products tested all yielded sequences that could be assigned to tissue transglutaminase (EC 2.3.2.13; tTG). In order to prove that tTG obtained from the fibrosarcoma cells binds to the endomysial antibody fraction of coeliac serum IgA, the authors performed indirect immunofluorescence with high titre coeliac disease serum samples on monkey oesophagus with or without prior incubation of those samples with a commercially available tTG extract (Sigma, Deisenhofer, Germany). Pretreatment with tTG almost completely abolished endomysial antibody labelling. Also, when the Sigma tTG was used as antigen in an enzyme linked immunosorbent assay (ELISA), 12 coeliac disease patient samples but none of the seven control serum samples displayed increased IgA immunoreactivity. Dieterich et al conclude they have identified tTG as the unknown endomysial autoantigen.