0212 - Immunopathology of Coeliac Disease Flashcards
Why is coeliac disease unusual?
It is an immune mediated disease (heavy lymphocyte infiltration), that is triggered by an exogenous antigen.
What is Coeliac disease?
A chronic, small-intestinal enteropathy which is triggered by gluten proteins from wheat, barley, and rye. Can trigger GI and extra-GI manifestations, including increased risk fo malignancy, particularly lymphoma (lymphocyte infiltration). Inflammation in the small bowel characterised by lamina propria inflammation with lymphocytes, villous atrophy, and crypt hyperplasia. Loss of villi surface area leads to significant absorption issues, and is the gold standard of diagnosis. Normal histology recovered after gluten-free diet.
What are the two HLA-antigens most associated with coeliac disease?
HLA-DQ2 and DQ8+. DQ2 present in around 95% of cases and has 8% risk of disease. However, these are neither necessary nor sufficient to cause coeliac disease (only 30-30% of genetic burden). Increased risk in homozygotes.
Briefly outline the pathophysiology of coeliac disease.
Gliadin remains as a 33-acid polymer post-digestion. This is deamidated by tissue transglutaminase (tTG) in brush border, and in turn is a substrate for tTG. Deamidated gliadin (33-mer) binds to T-cells even more efficiently than amidated, so the autoantigen makes the exogenous antigen even more immunogenic. APC binds to gliadin-tTG complex, and is activated by T4 recognising gliadin alone, leading to an activated immune response against tTG. Cycle, more gliadin->more tTG->greater immune response.
How is coeliac disease diagnosed?
Villous atrophy by endoscopy biopsy is gold standard. However, it is IgA-mediated, so it is diagnosable by blood test for anti-tTG antibodies, provided there is no IgA deficiency (which itself is associated with coeliac). Need to ensure they have sufficient IgA when attempting to diagnose by blood test. Can also test for anti-deamidated gliadin antibodies, but this is less sensitive except in <2 years. Antibodies should be undetectable after 3-6 months gluten-free.
