Human Leukocyte Antigen (HLA) refers to a group of genes that play a significant role in the immune system. These genes produce proteins located on the surface of most cells in the body. These HLA proteins help the immune system distinguish between the body’s own healthy cells and foreign substances like bacteria or viruses. Among these, HLA-DQ2 is a specific genetic marker that aids in this recognition process.
What is HLA-DQ2?
HLA-DQ2 is a specific variant within the Human Leukocyte Antigen (HLA) system, forming a protein complex on the surface of immune cells. The HLA system produces proteins that act as molecular “flags” on cell surfaces. These flags display small protein pieces, called peptides, to immune cells. It presents processed protein fragments to T-cells, a type of white blood cell that coordinates immune responses. This interaction helps the immune system identify and respond to various substances.
The Link to Celiac Disease
Possessing the HLA-DQ2 or HLA-DQ8 gene is strongly associated with celiac disease. About 90-95% of individuals with celiac disease carry HLA-DQ2, and most of the remaining 5-10% have HLA-DQ8. These genes are necessary for developing celiac disease; without them, the condition is highly unlikely.
However, inheriting HLA-DQ2 or HLA-DQ8 is not sufficient for celiac disease to manifest. Approximately 25-40% of the general population carries these genes, but only about 1-3% develop celiac disease. This indicates other factors, like gluten exposure and additional genetic influences, are also involved. In susceptible individuals, these HLA proteins bind and present specific gluten peptides to T-cells in the small intestine. This initiates an inappropriate immune response, leading to inflammation and damage to the intestinal lining characteristic of celiac disease.
Interpreting an HLA-DQ2 Positive Result
A positive HLA-DQ2 test result indicates a genetic predisposition for celiac disease. It means the person has the genetic potential for their immune system to react to gluten in a way that could lead to celiac disease. However, this result does not mean the individual currently has celiac disease or will definitely develop it. A positive HLA-DQ2 test is a risk factor, not a diagnosis.
For those with a positive result, it confirms the possibility of celiac disease, but further diagnostic testing is needed to determine if the condition is active. If symptoms like digestive issues, fatigue, or unexplained weight loss are present, a positive HLA-DQ2 result prompts further investigations. These include blood tests for celiac-specific antibodies and potentially an intestinal biopsy. Conversely, a negative HLA-DQ2 test result effectively rules out celiac disease. If an individual does not carry the HLA-DQ2 or HLA-DQ8 genes, the likelihood of having or developing celiac disease is extremely low, approaching 0.1%.
Testing for HLA-DQ2
Testing for HLA-DQ2 is a straightforward procedure, typically using a blood or saliva sample. This genetic test identifies the presence or absence of the HLA-DQ2 and HLA-DQ8 gene variants. Since these are genetic markers, results do not change over a person’s lifetime.
The primary use of HLA-DQ2 testing is to rule out celiac disease or assess genetic risk. It is useful when symptoms are atypical, there is a family history of celiac disease, or before a gluten challenge. A negative result can spare individuals from more invasive diagnostic procedures.