Celiac Disease – Celiac Disease

What is celiac disease?

Celiac disease is an autoimmune disorder that occurs in genetically predisposed individuals who develop an immune reaction to gluten. Celiac disease is a condition in which the digestive system is unable to break down certain foods, which is caused by gluten, which destroys the intestines of patients so that they cannot absorb the nutrients in the food. The disease mainly affects the small intestine, but the clinical manifestations are broad, with intestinal and extra-intestinal symptoms.

Symptoms of celiac disease

The symptoms of celiac disease appear after days to weeks of eating foods with gluten. Typical symptoms of celiac disease may include:

diarrhoea, weight loss and quite rarely delayed physical growth. Other symptoms include iron deficiency, bloating, constipation, chronic fatigue, headache, abdominal pain and osteoporosis.

Genetic Predisposition to Celiac Disease

The main environmental factor responsible for the development of celiac disease is gluten. Almost 100% of patients with celiac disease have specific variants of the HLA-DQ2 and DQ8 genes. More than 90% of patients with celiac disease are positive for DQ2 and the rest are positive for DQ8. It has been observed that the prevalence of DQ2 and DQ8 in patients with celiac disease shows geographical variability. The presence of HLA DQ2 and/or DQ8 is not in itself a diagnosis or prognosis of celiac disease. The presence of HLA-DQ heterodimers is present in about 25-30% of the white population. However, the risk of developing celiac disease in HLA DQ2/DQ8 carriers may increase to 3% instead of 1% in the general population.

Such cases include patients for whom histological examination suggests celiac disease, but who have negative serological tests and in people who already follow a gluten-free diet, or in people with an unclear diagnosis.

Given its genetic background, celiac disease runs in families. First-degree family members (parents, siblings, children) who share the same genotype as the family member with celiac disease have up to a 40% risk of developing celiac disease. The overall risk of developing celiac disease when the genotype is unknown is 7% to 20%.

How celiac disease is diagnosed

Gene testing

HLA-DQ2/DQ8 genotyping is very useful in excluding the possibility of celiac disease in certain clinical scenarios. A negative gene test rules out the possibility of developing celiac disease later, so this can be valuable information for first-degree family members. Genetic testing for celiac disease is recommended for family members, especially children.

However, the gene test alone cannot diagnose the disease – only 1 in 40 people who have HLA DQ2 or HLA DQ8 will develop celiac disease. A gluten-free diet should only be started after confirmation of celiac disease through cellular, gene and serological testing.

If all the above checks are negative. Then the last option is to do a small bowel biopsy.

The gene test is not affected by gluten intake, so it can be used when someone has already started a gluten-free diet. If the gene test is positive, then a gluten challenge followed by a small bowel biopsy will be required to check for celiac disease.

Serological control

An important step in the diagnostic approach to celiac disease is serological testing in the symptoms phase. Special immunological methods have been developed to diagnose specific antibodies in the serum of patients with celiac disease. The combined use of specific antibodies contributes to optimal diagnosis

1. Total immunoglobulin A (IgA).
2. Antibodies against unaminated gliadin peptides (anti-DGP) IgA/IgG
3. Antibodies against intramuscular (EMA) IgA
4. Antibodies against tissue transglutaminase (anti-tTG) IgA/IgG

Cellular control

Celiac disease has been clasiffied as a type IV (delayed) hypersensitivity reaction The Lymphocyte Transformation Test (LTT) is therefore a reliable, comprehensive tool for differential diagnosis.

Differences between Celiac Disease, gluten hypersensitivity and gluten allergy (cereals)

Cereals include four different types of proteins (albumin, globulins, prolamins and glutellins), and are one of the most common foods for inducing either a type I or type IV immune response. For example, gluten, a protein found in grains such as barley, wheat, oats and rye can cause various digestive symptoms, characterised by three different mechanisms: (a) allergic type (allergy to wheat; immediate type I reaction or type IV delayed type), (b) immunological type (celiac disease) and (c) non-immunological/allergic type (gluten hypersensitivity). Food allergic reactions may be of immediate type I, which are caused by mast cell degranulation, following IgE-mediated haemoglobin degranulation, and result in histamine release. Such reactions cause quite frequent episodes of anaphylaxis in patients. In these cases we expect a high percentage of specific IgE immunoglobulins against cereals and gluten in the serum of allergic/sensitised patients. On the other hand, food allergies may be delayed type IV reactions, involving specific memory T lymphocytes against foods and food extracts and causing a range of different symptoms such as angioedema, inflammation etc. Celiac disease as well as gluten hypersensitivity (not related to celiac disease) are involved in this category of reactions.

In patients with celiac disease where the Lymphocyte Transformation Test (LTT) was applied and who had not removed gluten from their diet, a reduced rate of T lymphocyte activation was observed after stimulation with a mitogenic agent, compared to patients who had excluded gluten from their diet, as well as to control patients.

On the other hand, gluten hypersensitivity is an idiopathic disease whose mechanism has not yet been described, but it seems that in this case an immune reaction to gluten and its products is induced with symptoms appearing after a few hours to days after consumption. The application of LTT in this case has shown that T lymphocytes from patients with symptoms similar to celiac disease but with negative serological tests, when incubated with gluten in vitro, result in positive LTT, i.e. high T lymphocyte activation compared to healthyt control patients.

In both cases, LTT can be a complementary tool for the diagnosis of these two diseases, in order to reduce the chances of invasive procedures in patients, which can be painful (e.g. gastroscopy).

Celiac disease and allergy to gluten (cereals)

• The possible diagnosis is based on the previous tests. A test can be positive (+) or negative (-) and the table above shows the hypotheses that leads to the possible diagnosis.