Coeliac disease

Question 1

Define coeliac disease

Answer 1

A common, chronic, immune-mediated, enteropathy that is triggered and maintained by ingestion of gluten in genetically-predisposed individuals

Question 2

what is enteropathy?

Answer 2

disease of the small intestine

Question 3

Histologically, what features are found in individual with Coeliac disease?

Answer 3

Duodenum has cracked appearance 
Intestinal inflammation: 
intraepithelial lymphocyte infiltration 
total villous atrophy (flattened appearance) - no villi
crypt hyperplasia

Question 4

what is crypt hyperplasia?

Answer 4

Grooves between villi are elongated

Question 5

what is total villous atrophy ?

Answer 5

erosion of intestinal villi

Question 6

List the gastrointestinal clinical symptoms of an individual with CD

Answer 6

Indigestion (dyspepsia)
Constipation
Diarrhoea
Vomiting
Bloating + flatulence 
Abdominal pain
Anorexia/weight loss

Question 7

List other extra intestinal symptoms sometimes found in those with CD

Answer 7

Anaemia
Bone weakness - osteoporosis, arthritis, fractures
Dermatitis herpetiformis - itchy skin
Delayed puberty 
Short stature - growth issues

Question 8

Discuss the aetiology of CD ****

Answer 8

Genetic susceptibility

trigger: Exposure to gluten peptides from grains including wheat, rye, and barley
* *******

Question 9

Gluten: a subtype of _____

Answer 9

prolamins

Question 10

What are prolamins and what type of amino acid do they have high levels of?

Answer 10

Prolamins = a group of plant storage proteins that have a high proline amino acid content

Question 11

what are the 2 components of gluten?

Answer 11

Gliadin (peptide component) and Glutenin

Question 12

Describe the pathophysiology of Coeliac disease (stage of gliadin moving into the lamina propria)

Answer 12

• High proline content of gluten makes it resistant to intestinal proteases.
• Undigested peptides can disrupt intestinal microbiota.
• When gliadin reaches the lumen of the small intestine, it binds to secretory IgA in mucosal membrane
• Usually substances bound to IgA are subject to immune destruction but in CD, Gliadin-IgA complex binds to transferrin receptor (overexpressed in CD)
• Once bound, it moves through enterocytes and into lamina propria.

Question 13

Describe the pathophysiology of Coeliac disease (“initiating inflammation” stage)

Answer 13

Once in the lamina propria: Tissue Transglutaminase (tTG) deamidates Gliadin (cuts off Amide) to Glutamate
• Deamidated gliadin is engulfed by macrophages (type of APC) and presented on MHC class II molecules to helper T cells

• MHC II “serving complexes” are coated in HLA genes (determines what thing to present)
• In those with CD, the MHC II complexes are coated in HLA-DQ2/8

• Helper T cells recognise the gliadin and release inflammatory cytokines to initiate inflammation. This causes destruction of enterocytes and villi

• T helper cells also recruit helper B cells to release Anti-Gliadin, anti-endomysial (EMA) and anti-tTG antibodies
• Killer T cells are also recruited which cause cell death and tissue remodelling with villous atrophy and crypt hyperplasia

Question 14

what is the main role of MHC class II molecules?

Answer 14

To present antigens to helper (CD4 )T lymphocytes

Question 15

What does the de-amidation of Gliadin peptide allow?

Answer 15

1) high-affinity binding to the coeliac-associated HLA peptides (DQ2 or DQ8) found on APCs
2) activation of helper T cells

Question 16

What HLA gene must be carried to develop coeliac disease?

Answer 16

Either HLA DQ2 (most common) or DQ8

Question 17

Describe the effect which coeliac disease has on iron haemostasis on the body

Answer 17

Those with CD have impaired duodenal mucosal uptake of iron since the surface absorptive area in the duodenum is reduced. This can cause iron deficiency and anaemia

Question 18

Describe the diagnosis of Coeliac disease

Answer 18

Serological test for:
Anti-tTG antibodies (first line – high specificity and sensitivity)
IgA antibodies (first line)
Anti-gliadin antibodies 
Anti-endomysial antibodies

Duodenal biopsy: obtained via endoscopy

Human Leucocyte Antigen (only undertaken in specialist settings)

Question 19

Can someone with an absence of HLA DQ2/8 have coeliac disease?

Answer 19

No

Question 20

If someone presents with CD symptoms and after conducting diagnostic tests their results come back positive for TTG and HLA DQ2/8 but not for the biopsy - what could be the possible reason for this?

Answer 20

Possible that biopsy result was incorrect/insufficient as the inflamed area could have been missed

Question 21

If someone presents with CD symptoms and after conducting diagnostic tests their results come back positive for biopsy and HLA DQ2/8 but not for the TTG - what could be the possible reason for this?

Answer 21

Patient could already be on a GF diet (TTG could be detected in blood by GP but there is a 6 month wait for the biopsy, so patient may get fed up and put themselves on a GF diet so TTG no longer positive)

Question 22

How is Coeliac Disease managed?

Answer 22

Gluten free diet (dietician review, free prescription for GF items in Scotland)

Nutritional assessment
Possibly: Bone health assessed via DEXA scan
Those with CD should have a Vaccination:
— Pneumococcus
— Meningococcus
(as they’re more at risk)

Question 23

25% of Coeliac patients are at risk of ____?

Answer 23

Osteoporosis

Question 24

What other health consequences does coeliac disease pose?

Answer 24

Hyposplenism (reduced spleen function) – risk of sepsis
Risk of Infection - reduced immunity
Increased risk of Non-Hodgkin’s Lymphoma (NHL) and small bowel adenocarcinoma
Increased overall mortality in adult life

Question 25

What is Refractory Coeliac Disease?

Answer 25

Presence of persistent symptoms and signs of malabsorption after gluten exclusion for 12 months with ongoing intestinal villous atrophy

Question 26

Out of RCD type 1 and type 2, which type has higher survival rates?

Answer 26

RCD type 1 has higher survival rates