primary prevention of coeliac disease - Associazione Italiana ...

Catassi C, Fasano A, Corazza GR (eds):
Primary prevention of coeliac disease. The
utopia of the new millennium? Perspectives on
Coeliac Disease, vol. 1, AIC Press, pp 89-92
The most recent advances on gluten
toxicity in coeliac disease
1 2 3
Gino Roberto Corazza , Carlo Catassi , Alessio Fasano
1
Department of Gastroenterology, University of Pavia, Italy;
2
Department of Pediatrics, University
3
of Ancona, Italy; Division of Pediatric Gastroenterology, Center for Celiac Research, University
of Maryland, Baltimore, MD, USA
After the Pavia meeting held on October 12, 2001, significant advances on the
possibilities of a primary prevention of coeliac disease have been achieved. While a part
of these have been recently published, most issues were discussed at the 10th
International Symposium on Coeliac Disease held at the Pasteur Institute in Paris, last
June.
The majority of these works deals with a further characterization of the gluten
peptides that trigger a T cell response. Although it is worth reminding that T cell
activation does not always mirror gluten toxicity in vitro or in vivo, the reportoire of
gluten peptides that are able to induce T cell activation seems now wider and more
heterogenous than reported at the Pavia meeting. At that time two different groups
found that a region of a-gliadin corresponding to aminoacids 57-75 acted as powerful,
immunodominant epitope if a glutamine residue (Q65) was deamidated by tissue
1-2
transglutaminase (tTG) to glutamic acid . Those findings disclosed new exciting
perspectives on possible alternatives for the treatment of coeliac disease, such as the
achievement of a non-toxic wheat by removal or modification of the above mentioned
antigenic sequences or specific immune therapy to induce oral tolerance.
Looking at the T cell profile in coeliac children with recent onset of disease,
3
Koning's group found that 6 novel additional gliadin and glutenin peptides were able
to induce T cell responses in the early phase of the pathogenesis of this condition. The
observation that immune activation was at some extent independent of deamidation
indicated that T cell responses can also be initiated by native gluten peptides. On the
basis of their results they estimated that gluten may contain up to 50 T-cell antigenic
peptide sequences (gliadin plus glutenin). No doubt that these results weakened the
4
expectations for new therapeutic approaches for this condition . In particular, as far as
the production of genetically detoxified grains is concerned, to the technical difficulties
listed by Biagi et al (pp 75-82 of this volume), the demonstration that glutenin peptides
are able to induce T-cell activation in coeliac disease makes the suggestion of
introducing high molecular weight glutenin genes to improve baking quality of maize
no longer tenable. On the other side, the observation that the number of peptides
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