13.11 Pathology: Coeliac Disease

Question 1

What is the prevalence of coeliac disease?

Answer 1

1:100 (likely 1:70)

Question 2

What are the genes associated with coeliac disease?

Answer 2

HLA-DQ2, HLA-DQ8

Question 3

Why isn’t B12 absorption affected in mild-moderate coeliac disease?

Answer 3

Coeliac disease affects the small intestine, B12 is absorbed further down

Question 4

What are the Valves of Kerkring?

Answer 4

Large valvular flaps projecting into the lumen of the small intestine

Question 5

What do the folds of Kerkring, the villi and the microvilli each increase surface area by?

Answer 5

3x
30x
600x

Question 6

What ratio of T-cells to enterocytes are considered abnormal in the duodenum?

Answer 6

> 25:100

Question 7

What 3 features do we see on a histological section of advanced Coeliac Disease?

Answer 7

• Total villous atrophy
• Crypt hyperplasia
• Intraepitherlial lymphocytosis

Question 8

What are the 3 stages in the development of villous atrophy with crypt hyperplasia (Marsh types)?
What are the villus to crypt length ratios of each type?

Answer 8

Type 1: Infiltrative (4:1, normal)
Type 2: Hyperplastic (1:1)
Type 3: Destructive (1:4)

Question 9

What role does environment play (specifically an infant diet) in coeliac disease?

Answer 9

Too much gluten too soon can increase risk

Question 10

How do T-cells produce damage in coeliac disease? (CD4 and CD8)

Answer 10

CD4+ T-cells (HLA-DQ2/8)
-reactive to gluten component–>IFN-y

CD8+ T-cells
-accumulate in epithelium, involved in innate immune response

Question 11

High content of proline means that it is more likely to___

Answer 11

Cross the epithelial barrier

Question 12

Intact peptides are ______ by ___ converting _______ residues into _ ____ ______

Answer 12

Intact peptides are deaminated by tissue transglutaminase (tTG) convertine glutamine residues into negatively charged glutamate

Question 13

How do these negatively charged peptides cause an immune response? (2 steps, APCs and MHC-II)

Answer 13

They bind more effectively to DQ2/8 molecules on APCs

The CD4+ T cells recognise the deamidated peptides (bound to MHC-II)–>cytokines

Question 14

What are 3 long term risks of untreated coeliac disease?

Answer 14

Osteoporosis, AI diseases and increased risk of cancer

Question 15

What type of cancer is associated with untreated coeliac disease?

Answer 15

EATL: Enteropathy associated T-cell lymphoma