The HLA-DQA1 gene is a component of the human immune system, located on chromosome 6. It provides instructions for making a protein that plays a role in distinguishing between the body’s own cells and foreign invaders like bacteria or viruses. This gene is part of a larger group known as the human leukocyte antigen (HLA) complex, which functions as an identification system. This process helps the immune system recognize threats and mount an appropriate response.
The Function of HLA-DQA1 in the Immune System
The protein produced by the HLA-DQA1 gene is part of the MHC class II complex. This complex is found on the surface of specialized immune cells, such as B lymphocytes, dendritic cells, and macrophages, known as antigen-presenting cells. These cells showcase small protein fragments, or peptides, derived from foreign invaders. The HLA-DQA1 protein combines with a protein from the HLA-DQB1 gene to form an antigen-binding DQαβ heterodimer.
When an antigen-presenting cell encounters a foreign substance, it breaks down the proteins into smaller peptides. These peptides are loaded onto the MHC class II complex and moved to the cell’s surface. Once displayed, these complexes present the foreign peptides to CD4+ T-cells. If T-cells recognize these peptides as foreign, they trigger immune responses to neutralize the threat. This process ensures the body effectively targets pathogens while avoiding harm to its own tissues.
Genetic Variations of the HLA-DQA1 Gene
The HLA-DQA1 gene exhibits significant genetic diversity across the human population. These different versions of the gene are known as alleles. Hundreds of distinct HLA-DQA1 alleles have been identified, each designated by a specific number, such as HLA-DQA1\05:01. These variations are a normal part of human genetic makeup.
The specific combination of HLA-DQA1 alleles an individual possesses influences how their immune system presents antigens. Common HLA-DQA1 alleles include \0101, \0102, \0103, and \0104, often found with specific HLA-DQB1 alleles, forming distinct haplotypes. While widespread, their presence alone does not indicate disease; instead, they influence immune system interactions with various substances. This genetic variability allows response to a broad spectrum of foreign invaders, but can also contribute to susceptibility to certain conditions.
Connection to Autoimmune Conditions
Certain variations, or alleles, of the HLA-DQA1 gene are associated with an altered risk for developing autoimmune conditions. In these situations, the immune system mistakenly identifies the body’s own proteins as foreign, initiating an attack on healthy tissues. The specific structure of the HLA-DQA1 protein, when combined with its HLA-DQB1 partner, can influence which peptides are presented to T-cells, sometimes leading to this self-directed immune response.
Celiac disease provides a prominent example, with a strong link to specific HLA-DQA1 alleles. Approximately 90-95% of individuals with celiac disease carry the HLA-DQ2.5 haplotype, which includes the HLA-DQA1\05 allele and HLA-DQB1\02. This combination forms a receptor that binds tightly to gluten peptides, leading to an inappropriate immune response and intestinal damage. Another significant risk haplotype for celiac disease is HLA-DQ8, involving HLA-DQA1\03 and HLA-DQB1\03:02, found in 5-10% of celiac patients.
Type 1 diabetes, another autoimmune condition, also shows a strong association with certain HLA-DQA1 alleles. The highest genetic risk is often observed in individuals inheriting specific combinations of HLA-DR3 and HLA-DR4 haplotypes. While these combinations significantly increase risk, protective HLA haplotypes also exist, which can lower the likelihood of developing type 1 diabetes.
Beyond celiac disease and type 1 diabetes, HLA-DQA1 alleles have been linked to other conditions. For instance, the HLA-DQA1\01:02 allele is strongly associated with narcolepsy type 1, an autoimmune sleep disorder where the immune system attacks orexin-producing neurons. Variations in this gene have also been implicated in certain allergies. Carrying these alleles increases susceptibility but does not guarantee disease development, as many people with these genetic predispositions remain unaffected.
Interpreting HLA-DQA1 Genetic Test Results
Genetic testing for HLA-DQA1, often performed alongside HLA-DQB1, is conducted using a blood sample or a cheek swab. For celiac disease, the test’s primary utility lies in its high negative predictive value. A negative result for the predisposing HLA-DQ2 and HLA-DQ8 haplotypes can effectively rule out the condition with nearly 100% certainty. This is helpful when symptoms are ambiguous or a patient has already begun a gluten-free diet before diagnosis.
Conversely, a positive result indicating the presence of high-risk alleles like HLA-DQA1\05 or HLA-DQA1\03 does not serve as a diagnosis for celiac disease or any other autoimmune condition. These genes are common in the general population, with about 35-40% of people carrying HLA-DQ2 and/or HLA-DQ8 without developing celiac disease. Therefore, genetic test results should always be interpreted by a qualified healthcare professional, considering them with a patient’s symptoms, family history, and other diagnostic evaluations, such as serological tests or biopsies.