Celiac disease, gluten sensitivity and wheat allergies 

Gluten-related disorders have gradually emerged as a major health care issue with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are different pathogenetic pathways involved in their development. 

The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient’s clinical history and specific tests, including blood tests and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. (see ref 1)

Celiac Disease is Inherited

Celiac disease tends to cluster in families. Parents, siblings, or children (first-degree relatives) of people with celiac disease have between a 4 and 15 percent chance of developing the disorder. However, the inheritance pattern is unknown. The risk of developing celiac disease is increased by certain variants of the HLA-DQA1 and HLA-DQB1 genes.

Non Celiac gluten sensitivity

Non-celiac gluten sensitivity” is the proposed definition for the condition in which gastrointestinal and extra-intestinal symptoms are triggered by gluten consumption, in the absence of celiac-specific antibodies and villous atrophy as well as of any allergy related processes

The clinical presentation of NCGS includes gastrointestinal symptoms, such as abdominal pain, bloating and altered bowel habit, and systemic symptoms, such as fatigue, headache, bone or joint pain, mood disorders and skin manifestations (e.g. eczema or rash). Symptoms usually closely follow the consumption of gluten and disappear after gluten withdrawal.

Contrary to CD and wheat allergy, there are no clear serologic or histopathologic criteria for clinicians to confirm the diagnosis of NCGS. The accurately CD detecting antibodies, namely TTG and EMA IgA, are constantly negative in NCGS. However, the presence of antigliadin IgG has been reported in up to 50% patients, while antigliadin IgA antibodies rarely occur (7%). 

The frequency of NCGS is higher in first-degree relatives of celiac patients and HLA-DQ2 and DQ8 genotypes are observed in 50% NCGS patients, which finding is mildly elevated in comparison with the general population.

In fact, oligosaccharides like fructans, contained in wheat and related grains, have been proven able to exert an osmotic effect in the intestinal lumen and increase gas production from bacterial fermentation. Other plant proteins contained in wheat, such as lectins, agglutinins and amylase-trypsin inhibitors, may have a role in the development of symptoms after the ingestion of cereals by triggering the innate immune response. For these reasons, and given the scattered data regarding the pathogenesis of NCGS, it has been suggested that the “non-celiac wheat sensitivity” definition may be more appropriate.