Human Leukocyte Antigens (HLA) are proteins found on the surface of most cells in the body, playing a fundamental role in the immune system. These proteins help the immune system distinguish between the body’s own healthy cells and foreign invaders like bacteria or viruses. They function as genetic markers, influencing how an individual’s immune system recognizes and responds to various substances. The specific variations in these HLA genes can impact an individual’s susceptibility to certain conditions.
Understanding HLA DQ8
HLA DQ8 is a specific genetic marker within the HLA system, which is part of the major histocompatibility complex (MHC) class II antigen-presenting receptor. HLA-DQ8 consists of two subunits, an alpha chain and a beta chain, which are encoded by the HLA-DQA1 and HLA-DQB1 genes respectively. This particular genetic variation influences the immune system’s recognition processes by presenting antigens to T-cells, a type of white blood cell. The structure of HLA-DQ8 includes a binding pocket that can hold small protein fragments, or peptides, from antigens. The way these peptides bind can determine if an immune response is triggered, influencing how the body differentiates between harmless substances and potential threats.
HLA DQ8 and Autoimmune Conditions
HLA DQ8 is commonly linked to autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues. It is a significant genetic factor associated with Celiac Disease and Type 1 Diabetes, acting as a risk factor rather than a sole cause.
In Celiac Disease, HLA-DQ8 contributes to genetic predisposition by binding to gliadin peptides, a component of gluten, more tightly than other antigen-presenting receptors. This tighter binding increases the likelihood of activating T lymphocytes, which initiates the autoimmune process in the small intestine. While HLA-DQ8 is present in roughly 8% of individuals with Celiac Disease, HLA-DQ2 is more common, found in about 90% of cases. However, HLA-DQ8 accounts for the majority of Celiac Disease cases not linked to HLA-DQ2.
For Type 1 Diabetes, HLA-DQ8 is the HLA serotype most linked to the disease. This genetic marker, especially in individuals who are heterozygous for both HLA-DQ2 and HLA-DQ8, shows a heightened risk. The HLA-DQ8 transdimer, formed in these heterozygous individuals, can bind and present unique auto-antigen-derived peptides, leading to the destruction of insulin-producing beta cells in the pancreas.
HLA-DQ8 also increases the risk for other autoimmune conditions, including rheumatoid arthritis, and is linked to the primary risk locus for rheumatoid arthritis, HLA-DR4. Additionally, there are less common associations with certain autoimmune thyroid diseases. The presence of HLA-DQ8, along with other genetic variations and environmental factors, collectively contributes to the overall susceptibility to these conditions.
Interpreting an HLA DQ8 Test Result
A positive HLA DQ8 test result indicates a genetic predisposition and an increased risk for developing certain autoimmune conditions, such as Celiac Disease or Type 1 Diabetes. However, having HLA DQ8 does not mean a person will definitively develop an associated autoimmune condition. For example, while about 25-30% of individuals of European descent carry HLA-DQ2, only about 4% of these individuals will develop Celiac Disease in their lifetime.
The likelihood of developing Celiac Disease in individuals with a positive genetic result approaches 40% if there is a known first-degree relative with the condition. Other contributing factors, such as environmental triggers and other genes, play a role in whether the condition manifests. A negative result for HLA DQ8, especially when combined with a negative result for HLA-DQ2, makes the development of Celiac Disease highly unlikely, with a probability greater than 99%.
Genetic Testing and Next Steps
HLA DQ8 testing is performed through a blood test or a cheek swab, as the results are not influenced by dietary gluten consumption. This genetic test analyzes the HLA-DQ2 and HLA-DQ8 haplotypes. The common reasons doctors recommend HLA DQ8 testing include screening for Celiac Disease in at-risk individuals, such as those with a family history of the disease, or as part of a diagnostic workup for autoimmune conditions. It is also useful when other test results are inconclusive or if a person has already started a gluten-free diet before being tested.
For individuals who test positive for HLA DQ8, it signifies a genetic predisposition, but not a definitive diagnosis. Such individuals, especially those with a family history of Celiac Disease, may be advised to undergo regular antibody screening every 2-3 years or immediately if symptoms develop. Further diagnostic testing, such as blood antibody tests or intestinal biopsies, would be considered to confirm an active condition. Consulting a healthcare professional, like a gastroenterologist specializing in Celiac Disease, is important for personalized advice and to interpret the results in the context of an individual’s overall health and symptoms.