Celiac Disease — Diagnosis & Management
HLA-gluten pathogenesis, serologic testing, biopsy strategy (Marsh classification), GFD adherence, and refractory CD with EATL risk.
HLA, gluten, and immune activation
Celiac Disease — Definition & Pathogenesis
Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by dietary gluten in genetically susceptible individuals. It is one of the most common chronic conditions worldwide, with a global prevalence of ~1%.
The Pathogenic Triad
Genetic Susceptibility
HLA-DQ2 (HLA-DQA1*05 / DQB1*02) — present in ~95% of CD patients. HLA-DQ8 (DQA1*03/DQB1*0302) — present in ~5%. Both confer antigen-presenting capacity for gliadin peptides.
Environmental Trigger
Gluten — storage proteins in wheat (gliadin), barley (hordein), and rye (secalin). Oats contain avenin — tolerated by most CD patients when certified pure.
Immune Activation
Tissue transglutaminase (tTG) deamidates gliadin → enhanced binding to HLA-DQ2/8 → adaptive T-cell response → villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis.
Epidemiology & Risk Groups
HLA Testing
Negative HLA-DQ2 and HLA-DQ8 has a >99% negative predictive value for celiac disease — excellent for ruling out CD in complex cases or family members.
Rubio-Tapia A et al. Am J Gastroenterol 2023;118(1):59-76