Celiac disease is an autoimmune condition primarily affecting the small intestine, triggered by the consumption of gluten, a protein found in wheat, barley, and rye. When individuals with celiac disease ingest gluten, their immune system mistakenly attacks the lining of the small intestine, leading to damage. This damage impairs the intestine’s ability to absorb nutrients, potentially causing various symptoms and complications. While environmental factors contribute to its development, a genetic predisposition involving specific human leukocyte antigen (HLA) genes is a significant component in celiac disease susceptibility.
The Role of HLA Genes
Human Leukocyte Antigen (HLA) genes are central to the immune system, helping the body distinguish its own cells from foreign invaders. These genes produce proteins on cell surfaces that identify what belongs in the body. They are part of the major histocompatibility complex (MHC) system, essential for immune response.
Nearly all individuals with celiac disease carry specific variants of these genes, primarily HLA-DQ2 and HLA-DQ8. About 90-95% have HLA-DQ2, while most others carry HLA-DQ8. Possessing these genetic markers indicates a predisposition to celiac disease, but does not guarantee its development. Many people (30-40% of the general population) carry these genes without ever developing the condition.
The HLA Typing Process
HLA typing is a genetic test that identifies specific HLA gene variants, such as HLA-DQ2 and HLA-DQ8. It typically involves a simple blood test or a cheek swab. For a cheek swab, a healthcare provider collects cells from inside the mouth.
The collected sample is sent to a specialized laboratory for analysis. There, the DNA is examined to determine the individual’s HLA type. This testing does not require special patient preparation, such as fasting. The procedure identifies genetic markers associated with celiac disease susceptibility.
Understanding Your HLA Test Results
Interpreting HLA typing results for celiac disease is straightforward for ruling out the condition. A negative result, indicating the absence of both HLA-DQ2 and HLA-DQ8 genes, means celiac disease is highly unlikely to develop. This is because almost all individuals with celiac disease carry at least one of these genetic markers. Therefore, a negative HLA test has a high negative predictive value, effectively ruling out the condition.
Conversely, a positive result, indicating the presence of HLA-DQ2 and/or HLA-DQ8, signifies a genetic predisposition for celiac disease. However, this positive result is not diagnostic of active celiac disease itself. A positive test only shows susceptibility. Additional diagnostic tests, such as blood antibody tests and intestinal biopsies, are necessary to confirm an active celiac disease diagnosis.
When HLA Typing is Recommended
HLA typing serves as a valuable tool in several specific clinical scenarios related to celiac disease. One common recommendation is to rule out celiac disease, particularly in individuals who have already adopted a gluten-free diet, which can make traditional antibody tests unreliable. For these individuals, a negative HLA test can confidently exclude celiac disease, eliminating the need for further diagnostic procedures or a gluten challenge.
The test is also useful for screening at-risk relatives, such as first-degree family members. Since celiac disease has a genetic component, testing relatives identifies those without predisposing genes, sparing them unnecessary screenings. HLA typing can also clarify uncertain diagnoses when initial antibody tests are inconclusive or biopsies show equivocal results. It can also be considered before a gluten challenge to assess genetic risk and potentially avoid the challenge if genes are absent.