Unexpected role of surface transglutaminase type II in celiac disease

Background & Aims: In celiac disease (CD), transglutaminase type II (TG2) has 2 fundamental roles: (1) as the autoantigen recognized by highly specific autoantibodies and (2) the modifier of pathogenic gliadin T-cell epitopes. It follows that inhibition of TG2 might represent an attractive strategy to curb the toxic action of gliadin. Here we studied the validity of this strategy using the organ culture approach. Methods: Duodenal biopsy specimens from 30 treated patients with CD, 33 untreated patients with CD, and 24 controls were cultured with or without gliadin peptides p31-43, pα-9, and deamidated pα-9 for 20 minutes, 3 hours, and 24 hours. In 31 patients with CD and 16 controls, TG2 inhibitor R283 or anti-TG CUB 7402 or anti-surface TG2 (6B9) mAbs were used in cultures. T84 cells were also cultured with or without peptides with or without TG inhibitors. Mucosal modifications after culture were assessed by immunofluorescence, in situ detection of TG activity, confocal microscopy, and fluorescence-activated cell sorter analysis. Results: The enzymatic inhibition of TG2 only controlled gliadin-specific T-cell activation. The binding of surface TG2 contained gliadin-specific T-cell activation and p31-43-induced actin rearrangement, epithelial phosphorylation, and apoptosis, both in organ cultures and T84 cells. Conclusions: These data indicate a novel and unexpected biological role for surface TG2 in the pathogenesis of CD suggesting a third role for TG2 in CD. These results have a specific impact for celiac disease, with wider implications indicating a novel biologic function of TG2 with possible repercussions in other diseases. © 2005 by the American Gastroenterological Association.

Decomposition of the B2-type matrix

The microstructural stability of aluminide diffusion coatings, prepared by means of a two-stage pack-aluminization treatment on single-crystal nickel-base superalloy substrates, is considered in this article. Edge-on specimens of coated superalloy are studied using transmission electron microscopy (TEM). The effects of coating thickness and post-coating heat treatment (duration, temperature, and atmosphere) on coating microstructure are examined. The article discusses the partial transformation of the matrix of the coating, from a B2-type phase (nominally NiAl) to a L12 phase (nominally Ni3(Al, Ti)), during exposure at temperatures of 850 °C and 950 °C in air and in vacuum for up to 138 hours. Three possible processes that can account for decom- position of the coating matrix are investigated, namely, interdiffusion between the coating and the substrate, oxidation of the coating surface, and aging of the coating. Of these processes, aging of the coating is shown to be the predominant factor in the coating transformation under the conditions considered. © 1992 The Minerals, Metals and Materials Society, and ASM International.