edited by Elisa Magnanelli M.D.
With the aim of analysing systematically the wide spectrum of gluten-related disorders, a gastroenterology think-tank has recently gathered for the "First International Consensus Conference on Gluten Sensitivity", held in London in February 11th and 12th, 2011, during which new nomenclatures (Figure 1) and diagnostic algorithms (Figure 2) have been proposed in order to bridge the gaps in existing classification.
According to new recommended classification, gluten-related disorders can be categorized depending on their pathogenetic mechanisms in:
Wheat, rice and corn are the most eaten cereals in the world. Wheat, the most widespread farming, is really diversified, with more than 25.000 varieties cultivated all over the world. A great part of world wheat production is consumed after having been transformed into bread and other baked products, pasta, noodles and, in Middle East countries and e Northern Africa, bulgur and couscous. Moreover, the wide availability of wheat flour and the functional properties of gluten proteins give reasons for their massive use as ingredient in food-processing.
Gluten is the main wheat protein composite; equivalent toxic proteins can be found in other cereals, including rye and barley. Gluten toxic proteins can be divided into two main fraction: gliadins, constituted of monomers, and glutenins, made up of protein aggregates.
It is possible that the introduction of gluten-containing cereals, occurred nearly 10.000 years ago with the advent of farming, represented an evolution challenge which created suitable conditions for the development of human gluten-related disorders; the most common of them are adaptive immune-mediate disorders: Wheat allergy and Celiac disease.
However it is getting more and more evident that the reactions to gluten does not include only Celiac disease, while we can actually identify the existence of a gluten-related spectrum disorders. The high frequency and the wide range of adverse reaction to gluten have driven researchers to investigate the reason why this food protein is toxic for so many people all over the world.
A possible explanation could be that the selection of most gluten-containing wheat variety was a continuous process during the last 10,000 years, when changes were brought about more by technology than by nutritional reasons. Wheat and its variety farming started thousands years ago; most of them -such as Triticum monococcum and t. dicoccum, containing less 33-mer gluten peptide, very toxic- have been used in human nutrition until the Middle Ages. As it seems, human organism is still exposed dangerously to the toxic effects of this protein complex, due especially to the lack of an effective gastrointestinal and immune defence mechanism adaptation.
Moreover, gluten is one of the most abundant and widespread food components for the main part of the population (of European origin in particular). In Europe, the average daily gluten intake is 10-20 grams, with subset of population consuming up to 50 grams or more of gluten every day. All individuals, even those at lower risk, are then susceptible to some form of gluten reaction during their life. Therefore, not surprisingly the last 50 years have witnessed an actual "epidemic" of celiac disease and the appearance of new gluten-related disorders, including the most recently identified Gluten Sensitivity.
As far as these pathologies are concerned, gluten reaction is mediated through activation of T cells in gastrointestinal mucosa. Nevertheless, in case of Wheat allergy it is the cross-linking between IgE and the repeated sequences in gluten peptides (e.g. Ser-Gln-Gln-Gln-[Gln]-Pro-Pro-Phe) to cause chemical mediators release, such as histamine, from basophils and mastocytes. On the contrary, Celiac disease is an autoimmune disorder, as shown by the presence of specific autoantibodies in serum, in particular anti tissue transglutaminase antibodies (tTG) and anti endomysial (EMA) antibodies.
In addition to Celiac disease andWheat allergy, cases of gluten reaction involving neither allergic nor autoimmune mechanisms also exist. They are generally defined as Gluten Sensitivity. People experiencing disorders while eating gluten-containing products and showing signs of improvement following a gluten-free diet, could be affected by Gluten Sensitivity rather than by Celiac disease. Patients suffering from Gluten Sensitivity can not tolerate gluten and develop adverse reaction when ingesting gluten-containing foods; nevertheless, gluten does not usually cause damage to small intestine unlike Celiac disease. Whereas gastrointestinal symptoms in case of Gluten Sensitivity are similar to those associated with Celiac disease, the overall clinical picture is not associated with the presence of tTG autoantibodies or other Celiac disease specific antibodies. Diagnosis is currently made by exclusion and an elimination diet or “open challenge” (i.e. consisting in the supervised reintroduction of gluten-containing foods) is more frequently used to evaluate whether the clinical picture improves eliminating or reducing gluten in diet. However, this approach is characterized by lack of specificity and risk of placebo effect due to the use of an elimination diet in order to improve symptoms.
The multiplicity of gluten-related disorders is related to the fact that our immune system reacts and fight against the ambient triggering factor (gliadin) in different ways.
In most of cases the information given by clinical picture will be enough to distinguish Wheat allergy from remaining two forms of gluten-related disorders. The determination of specific biomarkers for Wheat allergy and Celiac disease represent the first step in diagnostic process, consisting in gluten testing (regarding Wheat allergy) or intestinal biopsy (regarding Celiac disease). If the above mentioned forms have been excluded, just like other possible causes justifying the symptoms experienced by patients, then the diagnosis of Gluten sensitivity should be taken into consideration. A double-blind gluten test against placebo effects should represent the the final step in order to confirm or exclude the diagnosis of Gluten sensitivity.
Based on a set of clinical, biological, genetic and histological data it is possible to differentiate the three pathologies (Wheat allergy, Celiac disease and Gluten sensitivity) following the algorithm in Figure 2