Role of HLA-DQ2 and HLA-DQ8 Genes in Coeliac Disease

These genes encode proteins known as human leukocyte antigens (HLAs), which are responsible for presenting antigens to immune cells. In the context of coeliac disease, individuals who possess specific variants of the HLA-DQ2 (encoded by the HLA-DQA1 and HLA-DQB1 genes) and HLA-DQ8 (encoded by the HLA-DQA1 and HLA-DQB1 genes) genes are at an increased risk of developing the condition. These HLA molecules play a crucial role in initiating the immune response to gluten, the protein complex found in wheat, barley, and rye. Specifically, HLA-DQ2 and HLA-DQ8 molecules bind to gluten peptides that have been modified by tissue transglutaminase (tTG) within the gut lumen. This binding facilitates the presentation of gluten peptides to T lymphocytes, triggering an immune response characterized by inflammation and tissue damage within the small intestine.

These histological changes range from mild intraepithelial lymphocytosis ( an increase in the number of lymphocytes within the epithelial layer of the small intestine) to severe villous atrophy, reflecting the extent of damage to the intestinal mucosa caused by the autoimmune response to gluten. In coeliac disease, prolonged exposure to gluten triggers an immune-mediated attack on the intestinal mucosa, leading to damage and flattening of the villi. This results in a loss of surface area for nutrient absorption and can manifest as malabsorption-related symptoms such as diarrhea, weight loss, and nutrient deficiencies.

Treatment options for coeliac disease primarily revolve around the adoption of a strict gluten-free diet. However, effectively managing associated nutrient deficiencies is also crucial for optimizing the health and well-being of individuals with coeliac disease. adherence to a gluten-free diet is essential for promoting healing of the intestinal mucosa, can lead to histological recovery and resolution of symptoms and prevent further damage. nutrient supplementation in nutrients such as iron, calcium, vitamin D and B12 may be needed to resolve nutrient deficiencies. Regular monitoring of nutritional status and growth parameters is important for identifying and addressing any ongoing nutrient deficiencies or growth delays and for preventing long-term health complications such as osteoporosis and anemia. dults with coeliac disease are at increased risk of osteoporosis due to malabsorption of calcium and vitamin D. Therefore, emphasis should be placed on optimizing bone health through adequate calcium and vitamin D intake, regular weight-bearing exercise, and bone density monitoring.

Non-Malignant Inflammation of the Small Intestine:clinical presentation: Persistent symptoms such as diarrhea, abdominal pain, and malabsorption despite adherence to a gluten-free diet. Diagnostic Considerations: Endoscopy with biopsy revealing ongoing inflammation and villous atrophy. Serological markers may remain elevated.

Enteropathy-Associated T-Cell Lymphoma (EATL): Clinical Presentation: Severe symptoms, including weight loss, abdominal pain, and gastrointestinal bleeding. Lymphadenopathy may be present. Diagnostic Considerations: Biopsy showing infiltration of abnormal T-cells in the intestinal mucosa. Imaging studies may reveal lymphoma involvement.

Collagenous Sprue: Clinical Presentation: Chronic diarrhea, weight loss, and malabsorption. Histological examination reveals subepithelial collagen deposition in the small intestine. Diagnostic Considerations: Endoscopic biopsy demonstrating collagenous thickening of the subepithelial layer. Alternative Diagnoses (Autoimmune Enteropathy, Common Variable Immunodeficiency, Drug-Induced Villous Atrophy): Clinical Presentation: Variable symptoms, including diarrhea, abdominal pain, and weight loss. History of autoimmune diseases or immunodeficiency may be present. Diagnostic Considerations: Comprehensive evaluation to rule out other causes of villous atrophy. Serological testing, imaging studies, and tissue biopsies may be necessary.