Coeliac disease (CD) is a chronic gluten-intolerance that occurs in genetically predisposed individuals. In sensitive individuals, the ingestion of gluten causes chronic inflammation of the small intestinal mucosa leading to villous atrophy and nutrient malabsorption. The prevalence of CD is estimated at about 1:100 in Caucasians, and it occurs more often in females with a gender ratio of about two-to-one. Furthermore, gluten intolerance is more frequent in at-risk groups, such as first-degree relatives of patients as well as individuals with specific genetic syndromes (Down, Turner, Williams) or autoimmune diseases (type I diabetes, thyroiditis and multiple sclerosis).
Coeliac disease is a multi-factorial disorder in which specific HLA-DQA1 and HLA-DQB1 alleles represent the major genetic predisposition. HLA typing allows a patient assessment of their relative CD risk. This means a positive test is indicative of genetic susceptibility but does not necessarily mean the disease is actively developing. A negative test result from Kashi Health’s genetic test for Celiac Disease is just as informative because gluten intolerance rarely occurs in the absence of specific HLA predisposing alleles.
Approximately 90% of CD patients possess DQA1*05 and DQB1*02(DQ2.5); 5-10% carry DQA1*03 and DQB1*0302 (DQ8); while about 5% of patients possess DQ2.x molecules, encoded by the DQB1*02 at-risk allele in the absence of the DQA1*05; and very rarely, CD patients carry different DQ molecules (DQX.x). Chart 1, shown below, identifies the risks with celiac-associated DQ markers. Figure 1, also shown below, illustrates the at-risk heterodimers for CD encoded by different combinations of DQA1 and DQB1 alleles.
The close association between CD and these HLA alleles is due to the fact that these disease-associated HLA-DQ molecules expressed on antigen-presenting cells specifically bind gluten-derived peptides that are modified by the enzyme tissue transglutaminase (tTG) and present them to intestinal CD4+ T cells. The resulting T cell response leads to the production of auto-antibodies directed against tTG and to the secretion of pro-inflammatory cytokines (mainly TNF-α and IFN-γ) with consequent mucosa atrophy and clinical manifestations.
Chart 1: Risk gradient, considering a disease prevalence of 1:100. Refer to Figure 1 for nomenclature (from Megiorni F et al, 2009).
Figure 1: CD at-risk heterodimers encoded by different combinations of DQA1 and DQB1 alleles (from Megiorni and Pizzuti, 2012).
Kashi Clinical Laboratories utilises a combination of PCR-SSO (polymerase chain reaction sequence-specific oligonucleotide typing) and SBT (sequence based typing) to determine the patient’s HLA-DQA and DQB genotype.
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We will send you the test kit with 3 buccal swabs. You need to send it back to Invivo Clinical via guaranteed 1 pm next day delivery at your own cost. The results come back to us and we will email them to you.
If you like to discuss the results we can do this in a separate consultation with Dr Frey.