Gluten Sensitivity Antibodies Cascade

Gluten is a protein found in wheat, rye and barley. Gliadin is the alcohol-soluble fraction of gluten that contains the bulk of the toxic components of gluten. It is resistant to degradation in the human upper gastrointestinal tract and is able to pass through the epithelial barrier of the intestine. Gluten sensitivity is a state of heightened immunological responsiveness to ingested gluten. It represents the spectrum of diseases with diverse manifestations such as enteropathy (celiac disease), dermatopathy (dermatitis herpetiformis), neurological disorders (ataxia and neuropathy), and may be underlying reason for many other nonspecific symptoms like anemia, chronic fatigue, joint inflammation and pain, migraines, depression, attention-deficit disorder, epilepsy, osteoporosis and osteopenia, infertility, recurrent fetal loss, vitamin deficiencies, short stature, failure to thrive, delayed puberty, dental enamel defects, and autoimmune disorders. Patients with gluten sensitivity are reported to have increased mortality and its prevalence in the general population is up to 12%.

Antibodies to deamidated gliadin peptide and tissue transglutaminase are specific to celiac disease while antibodies to native gliadin are present in patients with and without gastrointestinal manifestations and are serological evidence of gluten sensitivity. Another subset of patients may have gluten sensitivity expressed in the form of allergic reaction to foods containing gluten like wheat. All of those patient groups may benefit from gluten-free diet.

This screening profile is designed to aid in the diagnosis of different forms of gluten sensitivity.

Step One: The screening starts with testing for tTG IgA and DGP IgG.^1,2 When any or both of the results are positive, testing stops and the interpretive comment on the report would read: "Suggestive of celiac disease or other gluten-sensitive enteropathies. Subsequent testing for Endomysial Antibody, IgA [164996] and/or genetic testing for Celiac Disease HLA DQ Association [167082] may be indicated for further patient evaluation." When result is negative, testing will reflex to the second step.

Step Two: In the second step, the test for IgG antibodies to native gliadin (AGA) is performed. AGA currently remain the most sensitive markers of the whole spectrum of gluten sensitivity including all the extraintestinal manifestations.^1,3 When the result is positive, testing stops and the interpretive comment would read: "Suggestive of nonceliac gluten sensitivity. The patient may benefit from a gluten-free diet." When the result is negative, testing will reflex to the third step.

Step Three: In the third and last step, the test for wheat allergen-specific IgE is performed. Allergic reaction to wheat may mimic the clinical presentation of gluten sensitivity like celiac disease and is one of the common food allergies in children. The triggering agent, however, may not be just gluten but any other protein or combination of proteins found in wheat.⁴ Because wheat allergy patients may also be allergic to other grains with similar proteins like rye and barley,⁴ they will benefit from the gluten-free diet. When the result is positive, testing stops and the interpretive comment would read: "Suggestive of wheat allergy. The patient may benefit from a gluten-free diet." When the result is negative, testing stops and the interpretive comment would read: “Not suggestive of gluten sensitivity.”