Coeliac Disease L17

Question 1

Coeliac disease is an allergy to what foods? (4)

What do all these foods contain that the allergen is found within?

Answer 1

• Wheat
• Barley
• Rye
• Oats

Gluten

Question 2

Read

Clinical presentation of coeliac disease

• Weight Loss
• Diarrhoea & malabsorption
  
  • Some steatorrhea
  • NO blood, NO pain (in general, but is possible)
• Failure to thrive
• Can be:
  
  • Asymptomatic
  • Mistaken for/or seen in IBD

Question 3

Through what technique are most coeliac sufferers diagnosed?

Answer 3

Antibody testing.

Question 4

What is the main difference between a healthy individual and a coeliac patient?

What does this cause?

Answer 4

The villi in coeliac patients have deteriorated (flattened) - villous blunting.

They therefore have a much lower surface area for absorption in the gut. This leads to stunted growth because they cannot absorb sufficient nutrients from the diet.

Question 5

State the sequence from deteriorated villi → failure to thrive in coeliac disease. (1→7)

Answer 5

1. Deteriorate villi
2. Less SA
3. Less absorption
4. Less nutrients reach the tissues
5. Less energy available
6. Less growth
7. Failure to thrive

Question 6

Describe the results of a duodenal biopsy on a coeliac disease sufferer.

Answer 6

• Flat mucosa
• Sub-total villous atrophy
• Villous blunting
• Increased intra epithelial lymphocytes
• Loss of small bowel surface area

Question 7

Describe the mechanism of the upper jejunal mucosal immunopathology of coeliac disease. (1→6)

Answer 7

1. Lymphocytes are recruited into the villi
2. Inflammation is starting to occur
3. Villi start to break down
4. Lymphocyte count keeps increasing
5. Other immune cells are recruited to the area as would be expected during inflammation
6. Villi become progressively flattened

Overall:

1. As immune cell numbers rise in villi
2. Inflammation escalates
3. Villi break down

Question 8

How is coeliac disease treated?

Answer 8

Gluten free diet

Question 9

List some of the adverse effects of coeliac disease. (8)

Answer 9

• Malnutrition
• Weight Loss
• Decreased Bone Mineral Density
• Autoimmune Disorders
• Miscarriages
• Anaemia
• Hypo-splenism – Treat with Pneumovax II
• Non-Hodgkins Lymphoma - Fatal

Question 10

Define refractory coeliac disease (RCD).

Answer 10

Persistent or recurrent malabsorptive symptoms and villous atrophy despite strict adherence to a gluten-free diet (GFD) for at least 6–12 months in the absence of other causes of non-responsive treated celiac disease (CD) and overt malignancy.

Question 11

State the mechanism of coeliac disease from gluten consumption to villous atrophy. (1→10)

Answer 11

1. Gluten is consumed
2. Is broken down and absorbed from the gut
3. Is picked up by an antigen presenting cell (APC)
4. Gluten antigen presented to HLA molecules
5. This activates CD4 T cells
6. CD4 T cells send out a range of signals (activate more T cell production, inflammatory responses etc.) and activate B cells
7. B cells produce antibodies
8. Antibody based response occurs (this is why antibody testing can be used as a diagnostic tool)
9. T cell inflammatory activation causes immune cell congregation and damage own cells
10. Villous atrophy

Question 12

Define concordance (genetics).

Answer 12

The probability that a pair of individuals will both have a certain characteristic, given that one of the pair has the characteristic.

Question 13

~30% of northern European Caucasians carry the HLA DQA1 and DQB1 alleles that encode the expressed HLA DQ2 molecule, BUT only ____% of these develop coeliac disease.

In most cases this is expressed in “cis” from the same parental haplotype - however in southern Europeans it is more likely to be expressed in “trans” from a combination of the parental haplotypes with the α-chain form one parent and the β-chain from the other.

90% of Coeliac patients have DQ2, whilst 10% have DQ8.

Answer 13

1

Question 14

The HLA group of genes have a very significant role in an individual’s risk of coeliac disease. HLA (Human Leukocyte Antigens) are present on the ____1____ of all cells apart from RBCs. HLA genes encode DQ molecules. These genes are the DQA and DQB genes. Each parent gives you one of each. DQA encodes the ____2____ chain of the DQ molecule and DQB encodes the ____3____ chain. Both chains come together to form the DQ molecule on the cell surface. These DQ molecules present short antigenic peptides (13-21 aa) to T cells. They achieve this presentation through APCs (HLA on APC surface). This stimulates the immune response. It appears that people who have coeliac disease have a higher frequency of encoding DQA1 and DQB1 that form a DQ2 molecule. Mum gives DQA and DQB, Dad gives DQA and DQB. Therefore to form a DQ2 molecule (in most cases) by having an A and a B, the inheritance of these alleles must come from a single parent – cis.

Answer 14

1. Surface
2. Alpha
3. Beta

Question 15

When does Coeliac disease present?

Answer 15

Mostly presents in childhood but can appear later in life.

Question 16

Why is coeliac disease more common in Europe compared to Asia?

Answer 16

Gluten is a staple of the european diet in foods such as bread.

This is not the case in Asia where rice (gluten free) is predominantly eaten instead.

Question 17

• The function of HLA DQ2 is to present gluten peptides to ___1___ cells
• HLA DQ2 heterodimer binds gluten peptide (___2___) with high affinity

Answer 17

1. T
2. α-gliadin

Question 18

Define shared disease genetics.

Answer 18

Genetics that increase susceptibility in one disease also effect the susceptibility in another. This is likely why we see people with one illness have an above average risk of developing another.

Question 19

Coeliac Pathology

Question 20

Read

Mucosal Disease

• Gluten reactive CD4+ T cells
• Release pro-inflammatory cytokines IFNγ
• This drives MMP secretion and cytotoxicity against enterocytes
• Resulting in villous flattening
• Other pathways include IL-15