Abstract
BackgroundIn celiac disease gluten, the disease-inducing toxic component in wheat, induces the secretion of autoantibodies which are targeted against transglutaminase 2 (TG2). These autoantibodies are produced in the small-intestinal mucosa, where they can be found deposited extracellularly below the epithelial basement membrane and around mucosal blood vessels. In addition, during gluten consumption these autoantibodies can also be detected in patients' serum but disappear from the circulation on a gluten-free diet. Interestingly, after adoption of a gluten-free diet the serum autoantibodies disappear from the circulation more rapidly than the small-intestinal mucosal autoantibody deposits. The toxicity of gluten and the secretion of the disease-specific autoantibodies have been widely studied in organ culture of small-intestinal biopsy samples, but results hitherto have been contradictory. Since the mucosal autoantibodies disappear slowly after a gluten-free diet, our aim was to establish whether autoantibody secretion to organ culture supernatants in treated celiac disease patient biopsies is related to the duration of the diet and further to the pre-existence of mucosal TG2-specific IgA deposits in the cultured biopsy samples.ResultsIn the organ culture system conducted with biopsies derived from treated celiac disease patients, gliadin induced secretion of autoantibodies to culture supernatants, reduced epithelial cell height and increased the density of lamina proprial CD25+ cells. However, these changes could be demonstrated only in biopsies from short-term treated celiac disease patients, where the small-intestinal mucosal TG2-specific IgA autoantibody deposits were still present. Furthermore, in these biopsies autoantibody secretion could be stimulated fully only after a 48-hour gliadin challenge.ConclusionOur results show that studies focusing on the toxic effects of gliadin in the organ culture system should be carried out with biopsy samples from short-term treated celiac disease patients who are likely still to have mucosal IgA deposits present. In addition to providing an explanation for the discrepancies in previous publications, the present study also enables further validation of the organ culture method.
Highlights
In celiac disease gluten, the disease-inducing toxic component in wheat, induces the secretion of autoantibodies which are targeted against transglutaminase 2 (TG2)
It has been suggested that endomysial autoantibody (EmA) secretion to the organ culture system is totally independent of gliadin challenge [18] and histological damage [14]. Due to these discrepancies among previous studies concerning autoantibody secretion to the organ culture system, our aim was to establish in both short- and long-term treated celiac disease patients whether the antibody secretion to culture supernatants is dependent on the duration of patients' gluten-free diet (GFD)
When the small-bowel biopsies from celiac disease patients were challenged in the organ culture system with peptic-tryptic digest of gliadin (PT-gliadin) for 48 hours, EmA was secreted to the culture supernatants in all five untreated but in only 11 out of the 20 treated celiac cases (Table 1)
Summary
The disease-inducing toxic component in wheat, induces the secretion of autoantibodies which are targeted against transglutaminase 2 (TG2) These autoantibodies are produced in the smallintestinal mucosa, where they can be found deposited extracellularly below the epithelial basement membrane and around mucosal blood vessels. After adoption of a gluten-free diet the serum autoantibodies disappear from the circulation more rapidly than the small-intestinal mucosal autoantibody deposits. In addition to causing damage to the mucosa in genetically susceptible individuals, gluten provokes the production of autoantibodies typically found in the sera of untreated celiac disease patients. These autoantibodies recognize exclusively endomysial antigens identified as transglutaminase 2 (TG2). At the time the autoantibodies have disappeared from the circulation, there may still be residual autoantibody deposits present in the small-intestinal mucosa which will in due course disappear on a strict gluten-free diet [4,6]
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