Celiac 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).
Celiac disease is a multifactorial 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).
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.
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.
Downloads: Sample Report