The introduction of cereals in human nutrition 10 000 years ago caused the occurrence of gluten induced diseases. This protein complex is involved in pathogenesis of wheat allergy, celiac disease, and gluten sensitivity.
Wheat allergy and celiac disease are mediated by the system of adaptive immunity. Gluten sensitivity is a recently defined entity induced by innate immune mechanisms.
These subjects present various intestinal and particularly extraintestinal symptoms. The differences between celiac disease and gluten intolerance include permeability of the intestinal mucosal barrier, histology of duodenal biopsy, and mucosal gene expression.
The symptoms of gluten sensitivity may also have another genetic background of food intolerance independent of the HLA-DQ2, -DQ8 system and tissue transglutaminase (eg. in some psychiatric disorders). At present, there is no specific biomarker of gluten sensitivity.
The diagnosis is possible only by exclusion of other causes of symptoms and improvement on a gluten-free diet applied in a double-blind placebo controlled manner with optional sequence of both stages to exclude the placebo effect due to nutritional intervention.