The human leukocyte antigen (HLA) system is a group of genes that play a role in the body’s immune defenses. HLA-DQ2 is a specific genetic marker forming a protein complex on the surface of immune cells. These HLA proteins act as molecular “flags” that display small protein pieces, known as peptides, to T-cells. This interaction helps the immune system identify and respond to various substances, distinguishing between the body’s own healthy cells and foreign invaders.
Understanding HLA Genes
HLA genes are located on chromosome 6 and are the most variable genetic system in humans. They are inherited from parents in a co-dominant manner, meaning both alleles (versions of a gene) are expressed equally. This allows individuals to express HLA molecules from both parents, enabling the immune system to recognize and respond to a wide array of pathogens.
HLA genes are inherited as a “haplotype,” a set of alleles passed down together on the same chromosome. The HLA system is divided into three main regions: Class I, Class II, and Class III. HLA-DQ2 is part of the Class II region, which primarily encodes genes expressed on antigen-presenting cells like dendritic cells, macrophages, and B cells.
The Link to Celiac Disease
The presence of HLA-DQ2, and to a lesser extent HLA-DQ8, predisposes individuals to celiac disease. Approximately 90-95% of individuals with celiac disease carry HLA-DQ2, with most of the remaining 5-10% having HLA-DQ8. These HLA proteins bind to and present certain gluten peptides to T-cells in the small intestine.
This binding triggers an inappropriate immune response, leading to inflammation and damage to the intestinal lining, which are hallmarks of celiac disease. The affinity of HLA-DQ2 for gliadin peptides, a component of gluten, is increased by tissue transglutaminase, an enzyme that modifies gluten peptides. HLA-DQ2.5 is strongly associated with the disease, while HLA-DQ2.2 is a lesser risk factor.
Inheriting HLA-DQ2 or HLA-DQ8 does not guarantee celiac disease. These genes are necessary but not sufficient for the condition to manifest. Other factors, including gluten exposure and additional genetic influences, also play a role. About 25-40% of the general population carries these genes, but only around 1-3% develop celiac disease.
Genetic Testing for HLA-DQ2
Genetic testing for HLA-DQ2 and HLA-DQ8 assesses an individual’s genetic predisposition for celiac disease. This test is useful when other diagnostic tests are inconclusive, or for screening family members of individuals diagnosed with celiac disease. Since HLA genes are genetic markers, results do not change over a person’s lifetime.
Testing involves a blood sample, or sometimes a cheek swab or saliva sample. Polymerase Chain Reaction (PCR) identifies the presence or absence of the HLA-DQ2 and HLA-DQ8 gene variants. This non-invasive approach can help avoid more invasive diagnostic procedures, such as intestinal biopsies, if a negative result is obtained.
What a Positive or Negative Result Means
A positive HLA-DQ2 test result indicates a genetic predisposition for celiac disease, meaning the individual possesses genes that could allow their immune system to react to gluten. However, a positive result is not a diagnosis; it confirms genetic potential. If a person has a positive result, further diagnostic testing, such as antibody tests and potentially an intestinal biopsy, is typically needed to determine if the disease is active.
Conversely, a negative HLA-DQ2 or HLA-DQ8 test result has a high negative predictive value for celiac disease, effectively ruling out the condition in almost all cases. If these genes are not detected, it is highly unlikely an individual will develop celiac disease in their lifetime, even with gluten consumption. Celiac disease can occur in less than 1% of cases without the typical HLA-DQ2 or HLA-DQ8 alleles. For family members of celiac patients, a negative genetic test provides strong reassurance, with a 99% probability they will not develop the disease.