301 Coeliac Disease

Question 1

Symptoms of coeliac disease

Answer 1

Bloating, diarrhoea, nausea, flatulence, constipation, tiredness, headaches, sudden weight loss, hair loss, anaemia, osteoporosis, rash (dermatitis herpetiformis), neurological disorder

Question 2

What can coeliac disease lead to?

Answer 2

Kidney & liver disease

Question 3

Mortality rate in untreated coeliac disease

Answer 3

Factor 1.9-3.8
Caused by link to malignancies

Question 4

What is gluten?

Answer 4

2 proteins: gliadin & glutenin
2 similar proteins in barley (hordeins) and rye (secalins)
10% wheat made up of gluten

Question 5

What is gluten involved in?

Answer 5

Starch storage in cell

Question 6

How much gluten can coeliac suffers tolerate?

Answer 6

20ppm so food must contain less than this to be “gluten free”

Question 7

Coeliac disease immune response to gluten:
Trigger
Immune activation
Antibodies
Result
Treatment

Answer 7

1. Gluten (from wheat, barley, rye) ingested
2. Modified gluten peptides trigger T cells
3. B cells produce anti-tTG and anti-gliadin antibodies
4. Inflammation damages intestinal villi, leading to malabsorption
5. Lifelong gluten-free diet

Question 8

How does immune response occur with gluten in coeliac disease?

Answer 8

T cells react with gluten peptides, especially gliadin), which has been modified by enzyme tissue transglutaminase (tTG)
B cells produce antibodies against gluten and tTG, resulting in inflammation

Question 9

Genetic predisposition for coeliac disease and immune response

Answer 9

People with genetic predisposition carry HLA-DQ2 or HLA-DQ8 genes which these T cells recognise gluten as a threat, becoming activated and launches immune response

Question 10

What is the mechanism of CD4 T-cell response to gliadin in coeliac disease?

Answer 10

Tissue transglutaminase (tTG) deamidates native peptides, creating modified peptides
These presented by DQ2/DQ8 on antigen-presenting cells, activating CD4 T-cells
Activation leads to interferon-γ release causing destructive intestinal lesions

Question 11

How does gluten trigger the immune response in coeliac disease?

Answer 11

Gluten-derived gliadin modified by tTG & presented by HLA-DQ2/8 on antigen-presenting cells
Activates T cells releasing IFNγ and promotes IL-15 expression
IL-15 stimulates NK-like cells to target intestinal cells, causing villi loss, crypt elongation & increased intraepithelial lymphocytes (IELs)
B cells produce antibodies against gliadin, endomysium & tTG

Question 12

Coeliac sufferers and their genetics

Answer 12

All have HLA-DQ2 (90%) or DQ8 genes (10%)
MHC II molecules binds negatively charged peptides
Gluten not negatively charged but can be deamidated by tTG
Gluten is proline rich so not digested well
A deamidated 33mer binds to MHC with high affinity

Question 13

Diagnosis of coeliac disease

Answer 13

Serum analysis for anti-gliadin/tTG antibodies
ELISA
Biopsy of intestine
HLA typing

Question 14

Therapeutic agent: genetically modified gluten and MOA

Answer 14

Decreases gluten exposure by transamidation of gliadin

Question 15

Therapeutic agent: zonulin inhibitor and MOA

Answer 15

Decreases zonulin secretion and inhibits intestinal permeability

Question 16

Therapeutic agent: therapeutic vaccine and MOA

Answer 16

Creates immune tolerance to gluten fragments & desensitises coeliac disease patients to toxic effects of gluten

Question 17

Therapeutic agent: probiotics and MOA

Answer 17

Detoxify gliadin & promote intestinal healing

Question 18

Therapeutic agent: tissue transglutaminase inhibitors and MOA

Answer 18

Stop tissue transglutaminases from modifying gluten fragments, a process that otherwise triggers immune response

Question 19

Aetiology of coeliac disease

Answer 19

1. Genetics: genetic markers HLA-DQ2/8, 95% of people carry these genes are coeliac
2. Environmental factors: gluten exposure, infections, early-life GI infections & gut microbiome imbalances
3. Immune system dysregulation: with genetic predisposition consuming gluten, inflammation trigger

Question 20

Nutritional implications: malabsorption

Answer 20

Damage to intestinal villi impairs nutrient absorption
Leads to vitamin deficiencies
Particularly if coeliac is untreated

Question 21

Nutritional implications: vitamin and mineral deficiencies

Answer 21

1. Iron: iron-deficiency anaemia due to impaired absorption which can lead to fatigue & weakness
2. vit B: folate, B12 & B6 affecting energy levels, nerve function & RBC production
3. Calcium & vit D: osteoporosis or osteopenia
4. Zinc and Mg: affecting immune & muscle function

Question 22

Nutritional implications: weight loss or growth issues

Answer 22

Children with untreated coeliac may experience stunted growth or delayed therapy
Adults may experience weight loss, weakness or muscle wasting

Question 23

Nutritional implications: fat malabsorption

Answer 23

Damage to intestine leads to difficulty absorbing fats
Leads to fat-soluble vitamin deficiencies (A, D, E, K) and symptoms like diarrhoea & steatorrhoea

Question 24

Nutritional implications: increased risk of lactose intolerance

Answer 24

Damage to intestinal lining may lead to 2ndary lactose (which digests lactose) is reduced when villi compromised

Question 25

Nutritional implications: risk of additional health conditions

Answer 25

Prolonged nutrient deficiencies can increase risk of anaemia, osteoporosis, neurological disorders and fertility issues