Describe the immunopathology of celiac disease and its effect on intestinal morphology.

• A. Autoimmune response to gluten (gliadin) leads to villous atrophy and crypt hyperplasia, especially in proximal small intestine, causing malabsorption.
• B. Bacterial infection causes villous blunting.
• C. Autoimmune reaction to lactose causes goblet cell hyperplasia.
• D. Inflammation limited to mucosa of colon.

Answer: (A)

The immune reaction to gluten in susceptible individuals drives damage to the small intestine. Gliadin peptides from gluten are deamidated by tissue transglutaminase, which enhances their presentation by HLA-DQ2/8 to CD4+ T cells. This activates an inflammatory response that damages the mucosa, especially in the proximal small intestine (duodenum and proximal jejunum).

Morphologically, this immunopathology causes villous atrophy (flattening of the finger-like villi) and crypt hyperplasia (deepened, proliferating crypts), along with a notable increase in intraepithelial lymphocytes. The result is a reduced absorptive surface area, leading to malabsorption of nutrients, iron, fat, and fat-soluble vitamins. The lesion pattern is characteristic of the proximal small intestine and is not limited to the colon or caused by bacterial infection or lactose-specific autoimmune reactions.