Celiac disease is an autoimmune condition triggered by gluten, a protein found in wheat, barley, and rye. When individuals with celiac disease consume gluten, their immune system mistakenly attacks the lining of their small intestine. This immune response leads to damage that can hinder nutrient absorption. Genetic factors play a significant role in determining who is susceptible to developing this lifelong disorder.
The Human Leukocyte Antigen System
The Human Leukocyte Antigen (HLA) system is a collection of genes located on chromosome 6 that play a central role in the immune system. These genes produce proteins found on the surface of most cells in the body. HLA proteins are responsible for helping the immune system distinguish between the body’s own cells (“self”) and foreign invaders like bacteria, viruses, or even fragments of food proteins (“non-self”).
When the immune system encounters a foreign substance, HLA proteins bind to small pieces of these foreign particles and present them to T-cells, a type of white blood cell. This presentation acts like a flag, alerting T-cells to the presence of a potential threat. The T-cells then mount an immune response to eliminate the perceived danger.
Specific HLA Genes in Celiac Disease
Celiac disease is strongly linked to specific HLA genes, particularly HLA-DQ2 and HLA-DQ8. Over 95% of individuals with celiac disease carry either the HLA-DQ2 or HLA-DQ8 alleles. In some populations, HLA-DQ2 is more prevalent, found in approximately 86% to 93% of celiac disease patients, while HLA-DQ8 is present in about 3% to 8% of patients without DQ2.
These particular HLA types are highly efficient at binding to and presenting gluten peptides to immune cells. Their presence alone does not guarantee that an individual will develop the condition. For instance, HLA-DQ2 and DQ8 are also found in a significant portion of the general population, ranging from 20% to 40%.
Using HLA Genetic Testing
HLA genetic testing for celiac disease is primarily used to help rule out the condition. If an individual does not carry the HLA-DQ2 or HLA-DQ8 genes, the likelihood of developing celiac disease is very low. A negative test result can often prevent the need for more invasive diagnostic procedures.
Conversely, a positive HLA genetic test, indicating the presence of HLA-DQ2 or HLA-DQ8, does not confirm a celiac disease diagnosis. Instead, it signifies a genetic predisposition to the disease. Further testing, such as blood antibody tests and intestinal biopsies, is required if symptoms are present. The test is useful when an initial evaluation is inconclusive or when individuals are already on a gluten-free diet, which can make other diagnostic tests less accurate.
When Genes Aren’t Enough
While the presence of HLA-DQ2 or HLA-DQ8 genes is a prerequisite for celiac disease, they are not the only factors involved in its development. The disease arises from a complex interplay between genetic predisposition and environmental triggers. For example, specific gluten exposure events or infections are thought to play a role in activating the disease in genetically susceptible individuals.
Many people with these genes never develop celiac disease, indicating that other factors are needed for the condition to manifest. Research continues to explore other non-HLA genes and environmental influences that contribute to the complete picture of celiac disease development.