A 2-year-old child with failure to thrive has frothy, pale, bulky, foul-smelling stools. Duodenal biopsy shows flattened villi with villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes. Serology is positive for anti-tissue transglutaminase IgA. The pathogenesis involves:

• A Lactase deficiency leading to osmotic diarrhea
• B Autoimmune destruction of parietal cells
• C Bacterial overgrowth with deconjugation of bile acids
• D HLA-DQ2/DQ8-restricted T-cell response to gliadin peptides ✓

Explanation

Celiac disease is an immune-mediated enteropathy triggered by dietary gluten (gliadin/glutenin fractions) in genetically susceptible individuals who carry HLA-DQ2 or HLA-DQ8 alleles. Tissue transglutaminase deamidates gliadin peptides, increasing their affinity for HLA-DQ2/DQ8 on antigen-presenting cells, triggering a CD4+ T-cell response with mucosal damage. The resulting villous atrophy leads to malabsorption, and the histological changes are reversed by a strict gluten-free diet.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.