Genetic predisposition to celiac disease Human leukocyte antigen – HLA – DQ2/DQ7/DQ8

General Information

Celiac disease is a chronic autoimmune inflammatory disease of the digestive system, the development of which is initiated by eating gluten. The condition lasts throughout life.

autoimmune inflammation develops during celiac disease; In particular, transglutaminase present in the cells of the intestinal wall interacts with gliadin received from food and forms complexes. The resulting complex is a powerful antigen against which the production of specific T lymphocytes begins.

Since only specific HLA antigens (Human Leucocite Antigens) bind to gliadin, the disease develops in people carrying these HLA antigens. This explains the family nature of the disease. The frequency of the disease is more than 10% in first-degree relatives, and 70% in monozygotic twins.

Celiac disease is not a rare disease, it is 2-3 times more common in women.

Class II HLA antigens are known to predispose to celiac disease HLA-DQ2 , HLA-DQ8 , DQ7 in the name They are synthesized by the corresponding genes.

It is found in 90-95% of celiac patients HLA-DQ2 , and in the remaining 5% HLA-DQ8  antigens. In addition, patients have the presence of other HLA antigens,

HLA-DQ2 and HLA-DQ8 genes play a crucial role in the development of celiac disease. These genes are part of the human leukocyte antigen (HLA) system, which is involved in the immune response.

Genetic predisposition: The presence of HLA-DQ2 or HLA-DQ8 genes increases the risk of developing celiac disease. However, it is important to note that not all people with these genes develop celiac disease.

immune response: As with other autoimmune diseases, celiac disease develops in genetically predisposed individuals (with specific HLA antigens) in response to gluten ingestion. The immune system reacts inappropriately to gluten, causing damage to the small intestine.

Autoimmune process: Celiac disease is an autoimmune disease, which means the immune system mistakenly attacks healthy tissue. The HLA-DQ2 and HLA-DQ8 genes are thought to play a role in this autoimmune process. Although these genes are strong risk factors for celiac disease, environmental factors must also play a role. Exposure to gluten is necessary for the condition to develop.

Although 30% of the world's population may have one of the genes predisposing to the development of celiac disease (DQ2 or DQ8), in order for the disease to develop, the presence of several genes is necessary, which is found in about 3% of the population.

The detection of alleles of HLA genes does not confirm the diagnostics of celiac disease, however, it indicates an increased risk of developing the disease. On the other hand, the absence of the corresponding allele of the HLA genes excludes the diagnostics of celiac disease.

When is the survey conducted?

Research is recommended in the following cases:

• Symptomatic patients with an equivocal response to a tissue transglutaminase antibody test also did not have an intestinal biopsy.
• In patients whose symptoms have dramatically decreased or practically disappeared after removing gluten from the diet;
• In symptomatic patients, when removing gluten from the diet does not produce results and does not reduce symptoms.
• For differential diagnostics in patients with symptoms similar to celiac disease
• in first- and second-degree relatives of patients with celiac disease

Research is important to rule out celiac disease and assess the risk of developing the disease.

Material for examination: Venous blood

Interpretation of results

A negative result for the predisposing HLA DQ2, DQ7 and DQ8 alleles practically excludes the diagnostics of celiac disease and indicates a minimal lifetime risk of developing the disease (<1%).

Identification of any pair of these HLA alleles in a person establishes a 3% cumulative risk of developing celiac disease.

In first-degree relatives of a person with celiac disease, the discovery of an allele of the predisposition genes increases the risk of developing the disease to 40%.

People with only the HLA DQ8 gene have a much lower risk of developing celiac disease than those with only the HLA DQ2 gene.

The detection of only HLA DQ8 or only HLA DQ2 gene does not make a difference in the clinical course of the disease.

It is estimated that people with both HLA-DQ2 and HLA-DQ8 genes have a lower risk of developing celiac disease than people with only the HLA DQ2 gene. However, the simultaneous presence of both types of antigens significantly increases the risk of developing the disease compared to the presence of the HLA DQ8 gene alone.