Overview
Why the Workup Depends on Gluten
Celiac disease is an immune mediated enteropathy triggered by dietary gluten in a genetically susceptible person.
Celiac disease is an immune-mediated enteropathy triggered by dietary gluten in a genetically susceptible person. HLA-DQ2 or HLA-DQ8 permits presentation of gluten-derived peptides; tissue transglutaminase deamidates those peptides, intensifying the immune response. The resulting inflammation damages the small-intestinal mucosa and can flatten the villi, reducing absorptive surface area. That mechanism explains why the presentation is broader than diarrhoea. Iron deficiency, fatigue, weight change, bloating, malabsorption, low bone density, infertility or adverse pregnancy outcomes may be the clinically visible part of the same intestinal injury. Symptoms alone cannot establish the diagnosis, and improvement after avoiding bread does not prove that celiac disease is present. The diagnostic pathway is therefore designed to answer two questions: is there an immune response to gluten, and is there compatible small-bowel injury? Removing gluten before answering either question can make both tests falsely reassuring.