Coeliac disease is a complex autoimmune disorder with a strong genetic component. In individuals with a genetic predisposition, the ingestion of gluten—a protein found in wheat, rye, and barley—triggers an immune response that damages the small intestine. This damage includes harm to the villi, bowel inflammation, and impaired nutrient absorption, leading to symptoms such as diarrhea, abdominal pain, and bloating.

The primary genes involved in coeliac disease are part of the major histocompatibility complex (MHC) located on chromosome 6p21. The MHC contains numerous human leukocyte antigen (HLA) genes, which encode glycoproteins that recognize peptides in immune cells. When these peptides are identified as foreign, they trigger cell apoptosis. In coeliac disease, the MHC genes that recognize and present gluten to T CD4+ cells encode the HLA-DQ8 and HLA-DQ2 receptors. HLA-DQ2 is composed of two subunits, α and β, which form the heterodimeric protein DQαβ. These subunits are encoded by the HLA-DQA1 and HLA-DQB1 genes, respectively.

Prevalence of HLA-DQ Genotypes

Approximately 90% of coeliac patients carry the HLA-DQ2 heterodimer (genotype HLA-DQA105 and HLA-DQB102). The remaining patients mostly carry the HLA-DQ8 heterodimer (genotype HLA-DQA103 and HLA-DQB103:02), which also triggers the immune response to gluten. There is a gene dosage effect for HLA-DQB102 and HLA-DQB103, making it important to report the genetic load (one or two copies). Coeliac disease affects an estimated 1 in 100 people worldwide, with many undiagnosed individuals at risk of long-term health complications. It can develop at any age after consuming gluten-containing food or medications. If untreated, it can lead to severe health issues. In children, malabsorption can also impact growth and development.

Role of HLA Testing in Diagnosis

As our understanding of coeliac disease has advanced, HLA testing has become an important diagnostic tool. It has been recently included in the new diagnostic guidelines for children and adolescents by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). While its inclusion in adult guidelines varies, HLA testing is generally used to support diagnosis in many cases.

The Imegen-Coeliac PCR Kit leverages a combination of oligonucleotides and fluorescent hydrolysis probes in a qualitative real-time PCR test. This test is validated for the simultaneous detection of the genotypes most frequently associated with a higher susceptibility to coeliac disease. Specifically, it detects alleles HLA-DQA105, HLA-DQA103, and HLA-DQB103:02, and enables allelic discrimination between HLA-DQB102 and other HLA-DQB1 alleles (DQB103, DQB104, DQB105, and DQB106).

This genetic test allows the user to determine the presence or absence of these genotypes through two multiplexed PCR reactions, which include amplifying the reference gene, β-globin, for DNA quantity and quality control. This advanced diagnostic tool enhances the ability to identify genetic predisposition to coeliac disease, supporting more accurate and timely diagnoses.