From the Guidelines
Genetic testing for celiac disease, specifically HLA-DQ2 and HLA-DQ8 genes, is most valuable as a rule-out tool and should be considered in cases where seronegative celiac disease is suspected or when the diagnosis is uncertain, as stated in the 2021 study 1. The test is particularly useful for people who have already started a gluten-free diet before being tested for celiac disease, for first-degree relatives of celiac patients, or when other test results are inconclusive. Some key points to consider when interpreting genetic testing results include:
- A negative result for HLA DQ2 and DQ8 effectively rules out celiac disease, as nearly 100% of individuals diagnosed with celiac disease exhibit this specific genetic profile, as mentioned in the 2024 study 1.
- A positive result, on the other hand, indicates an increased risk of developing celiac disease but does not confirm the diagnosis, as about 30-40% of the general population carries these genes but only 1% develops the condition, as noted in the 2021 study 1.
- The test requires a simple blood sample or cheek swab and doesn't require the patient to be consuming gluten, making it a convenient and non-invasive diagnostic tool.
- Genetic testing complements but doesn't replace other diagnostic methods like blood antibody tests and intestinal biopsies, as emphasized in the 2019 study 1.
- Clinicians should carefully evaluate all alleles tested and reported by the laboratory, including HLA DQ2.5, HLA DQ8, HLA DQ 2.2, and HLA DQ7.5, to ensure accurate interpretation of genetic testing results, as recommended in the 2021 study 1.
From the Research
Celiac Gene Testing
- Celiac disease is an immune-based reaction to dietary gluten that primarily affects the small intestine in those with a genetic predisposition 2.
- Genetic testing for human leukocyte antigen alleles DQ2 or DQ8 may be performed in select cases to support the diagnosis of celiac disease 3, 4.
- The presence of human leukocyte antigen alleles DQ2, DQ8, or both is essential for the development of celiac disease 4.
- Celiac disease can be diagnosed using a combination of serologic testing, duodenal mucosal biopsies, and genetic testing 2, 3, 4.
Diagnosis and Management
- The diagnosis of celiac disease is confirmed by duodenal mucosal biopsies and serologic testing of celiac-specific antibodies 2, 3.
- A gluten-free diet is the primary treatment for celiac disease, and patients may benefit from support groups and education on common and hidden sources of gluten 3, 4.
- Patients with celiac disease who do not respond to a gluten-free diet should have the accuracy of the diagnosis confirmed, have their diet reassessed, and be evaluated for coexisting conditions 3, 4.
Role of Tissue Transglutaminase
- Tissue transglutaminase (tTG) is a calcium-dependent ubiquitous enzyme that catalyses posttranslational modification of proteins and is released from cells during inflammation 5.
- tTG is suggested to exert at least two crucial roles in celiac disease: as a deamidating enzyme, that can enhance the immunostimulatory effect of gluten, and as a target autoantigen in the immune response 5.
- tTG IgA antibodies are a hallmark for celiac disease and are used to monitor patients with celiac disease on a gluten-free diet 6.