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 27-29
Role of A-gliadin 31 - 49 peptide
Paul J Ciclitira
The Rayne Institute, St. Thomas’ Hospital, London, UK
Coeliac disease was first described in 1888. Samuel Gee who gave a classic
description of a wasting disease mostly affecting children and causing diarrhoea,
concluded at the end of his treaties, "if the patient can be cured at all, it must be by means
of the diet". It is unfortunate that his treatment at that time comprised thin gruel which
contained wheat flour. It remained until 1953, for Professor Dicke and colleagues to
publish their findings that wheat, rye and barley exacerbated the condition. They also
noted that oats was toxic, which was probably due to contamination of flour with wheat.
Dicke's experiment at that time compromised of making a slurry of the individual flours
in water, pouring them down an eight year old child 's throat and noting that the child
collapsed with vomiting, diarrhoea and near death. They extended this work to show
that the most toxic component of wheat resides in the endosperm or flour fraction.
However, the germ and husk were mildly toxic. This was probably due to
contamination of these fractions with the gluten proteins.
Flour contains proteins and water soluble starch fractions. Purified wheat starch is
often used for the production of gluten-free products. Wheat flour proteins can be
divided into four groups of which gliadins and glutenins together comprise 90% of the
protein. The albumins and globulins are minor protein fractions. The glutenins have
molecular weights ranging from 50 kilodaltons to many millions and entrap carbon
dioxide in the dough enabling it to prove and rise. It was in early studies that the alcohol
soluble or gliadin fraction of gluten was shown to be toxic in coeliac disease. The
gliadin proteins were sub-divided into four fractions termed a, b, gand waccording to
their relative electrophoretic mobility. More recently, they were classified as a, g, and w
fractions according to their N-terminal amino acid sequences. We previously purified,
using column chromatography with 20 litres eluent, gliadin into its a,b, g, and w
fractions. The complexity of the individual gliadins was shown in further experiments.
Having made polyclonal anti-sera against each gliadin fraction, we looked for
precipitin lines on Ouchterlony gels which revealed four precipitin lines to gliadin, with
an anti-gliadin serum. Precipitin lines were shared between gliadin subfraction
suggesting that they share antigenic determinants. We subsequently used an in vitro
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