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 83-88
Immunotherapy of coeliac disease:
where do we stand?
1 1 1 1
Carmen Gianfrani , Mauro Rossi , Giuseppe Mazzarella , Francesco Maurano ,
2 2 2 2
Virginia Salvati , Delia Zanzi , Salvatore Auricchio and Riccardo Troncone
1 2
Institute of Food Sciences and Technology, CNR, Avellino, Italy; Department of Pediatrics
and European Laboratory for Food-Induced Disease, University Federico II, Naples, Italy
Introduction
Coeliac Disease (CD) is with little doubt an immune-mediated disease, triggered by
the ingestion of wheat gliadin and related prolamines from other toxic cereal such as
barley and rye. The hallmark of CD is the enteropathy characterized by an altered
morphology of villous architecture and severe malabsorption, but it is now very clear
1
that the disease affects not only the small intestine .
An important feature of CD is its strong genetic association with HLA class II genes:
more than 90% of patients carry the HLA-DQA*0501/DQB*0201 (DQ2) alleles,
whereas the majority of DQ2-negative patients are DQ8-positive
2
(DQA*0301/DQB*0302) . Among the non HLA genes that have been suggested to
contribute to the CD susceptibility so far, only the CTLA4 gene has been found
associated to coeliac disease in several populations examined. The strong genetic
association with HLA molecules is strengthened by the finding that gliadin-derived
peptides are recognized by coeliac intestinal lymphocytes when presented by the
disease predisposing DQ2 or DQ8 molecules. In fact, from the immunological point of
view, it is now generally accepted that a recognition of gliadin peptides in association
with HLA Class II molecules by Th1 T cells secreting proinflammatory cytokine leads
3
to the overt CD lesions at the intestinal level .
CD, in the great majority of cases, is efficiently cured by the gluten-free diet;
nevertheless, for some patients the diet is unpalatable and for others the compliance is
quite poor. For these reasons a more acceptable form of therapy would be desirable:
many efforts from our laboratory are focused on the development of conceptually
amenable therapeutic strategies. In particular, considering that CD is an immune
mediated pathology, any immunomodulatory strategy that could specifically block the
adverse immune reactions triggered by gliadin, represents a valid alternative to the
exclusion diet. Moreover, because the dietetic approach has a proven efficacy and
safety, the immunomodulatory therapy must be strictly antigen-specific, not affecting
the immune response to other antigens, and devoid of risks.
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