Settembre 2005 - Volume XXIV - numero 7
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Dipartimento di Scienze della Riproduzione e dello Sviluppo, IRCCS “Burlo Garofolo”, Trieste
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Dipartimento di Pediatria, Università “Federico II” di Napoli
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Scuola di Specializzazione in Pediatria, IRCCS “Burlo Garofolo”, Trieste
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Dipartimento di Pediatria, Università di Cagliari
Key words: Autoantibodies directed against actin filaments (AAA), Apoptosis
Recently, serum of celiac patients affected by autoimmune hepatitis revealed autoantibodies directed against actin filaments (AAA). The preliminary results regarding AAA showed a strong correlation between AAA antibody titre and the severity of intestinal damage. The AAA testing showed high specificity given that AAA are not found in specific conditions such as Crohn’s disease and autoimmune enteropathy. Further observations showed that the actin content of enterocytes increases if gluten is introduced in the colture. These data may suggest the possibility to avoid intestinal biopsy in case of AAA positivity, hence modifying the whole diagnostic protocol. At the same time, they may suggest that tissue transglutaminase lead to the development of gluten-dependent autoimmunity against actin with following tissue damage.
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Dipartimento di Scienze della Riproduzione e dello Sviluppo, IRCCS “Burlo Garofolo”, Trieste
Key words: Intestinal biopsy, ESPGHAN criteria
Usually the diagnosis of celiac disease is an easy task, thanks to the availability of good serology tests and to the intestinal biopsy, which represents a precious chance of looking at the gluten toxicity right in the gut. Although the significant improvement in the research field, biopsy is still required by the international protocol, in particular according to the ESPGHAN criteria. Intestinal biopsy offers the advantage of avoiding the gluten challenge and of promoting a better diet compliance, by giving a certain diagnosis. Moreover the biopsy can be useful in denying those cases in which a wrong diagnosis of celiac disease was put.
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Dipartimento di II Patologia Chirurgica, Spedali Civili, Brescia
Key words: Duodenal biopsy, Intraepithelial lymphocytes
When diagnosing celiac disease, the intestinal biopsy represents a moment of close collaboration between the pathologist and the clinician. The accuracy of the hystological diagnosis depends on the number and the adequate placement of the biopsies on the slides. It is fundamental to correctly interpret the biopsy in order to recognise artefacts and to describe the different mucosal strata, the relation between villus/crypt and the presence of intraepithelial lymphocytes. All these characteristics are of great help for the clinician in order to identify non clear celiac forms.
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Dipartimento di Scienze della Riproduzione e dello Sviluppo, Università di Trieste e IRCCS “Burlo Garofolo”, Trieste
Key words: Population based screening, High risk group screening
From the clinical and the epidemiological point of view, celiac disease may represent an appropriate disease model to apply a population based screening strategy. In the literature, the use of human tTG antibodies is described as an efficient screening strategy both in high risk groups and in family “case finding” series. However, population based screening is still a matter of debate, since it is yet not clear which is the most appropriate age when performing the screening and which motivations to offer to those subjects positive at the screening but still asymptomatic. It has been suggested to first identify subjects at risk by neonatal determination of HLA DQ2/DQ8 and to follow them up with periodical sierological tTG tests in order to identify early celiac patients.
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Dipartimento di Gastroenterologia, Università di Stanford, California (USA)
Key words: 33-mer peptide, Prolyl endopeptidase, Gliadin peptides
Many gluten peptides elicit T cell-proliferative responses in celiac patients. These peptides are rich in proline and glutamine residues and so extremely resistant to proteolysis. This resistance is related to their toxicity. A 33-mer peptide was identified as the primary initiator of the inflamnmatory response to gluten in celiac disease. In vitro and in vivo studies demonstrated its stability towards breakdown by all gastric, pancreatic and intestinal brushborder membrane proteases. This peptide reacts with tissue-transglutaminase with impressive selectivity and it is a potent inducer of gut-derived human T cells from celiac patients. Homologs of this peptide were found in all food grains that are toxic for celiacs but are absent from all non-toxic foods. The 33-mer peptide is detoxified by exposure to a bacterial prolyl endopeptidase, suggesting a strategy for oral peptidase supplement therapy for celiac disease in alternative to the gluten-free diet. A clinical trial to test the efficacy in vivo of endopeptidase added to gluten in preventing its multiform toxicity is ongoing.
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Istituto di Botanica e Genetica vegetale, Università Cattolica S. Cuore, Facoltà di Agraria, Piacenza
Key words: Gluten, Gliadine, Wheat genome, Wheat gene modifications
Many celiac patients find gluten free diet not tasty and difficult to follow rigorously. It is therefore auspicable to develop new gluten-free food products which taste better, including bread. Several attempts of gene modifications in order to eliminate allergic peptides from wheat have been made but unfortunately they did not lead to any significant result, given the complexity of wheat genome and the presence of a high number of toxic peptides. Ongoing experiments which genetically combine a non-allergic cereal (rice) with those wheat proteins which are necessary for the baking process, represent a new potential winning approach.
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