Coeliac Disease

Question 1

What is coeliac disease?

Answer 1

• Autoimmune disorder - characterised by gluten sensitivity
• Can be diagnosed at any age
• More prevalent in women

Question 2

What are the risk factors for coeliac disease?

Answer 2

Genetics (around 70% if monozygotic twin affected)
Autoimmune thyroid disease (15%)
Dietary gluten
Type 1 diabetes mellitus (8%)
IgA deficiency (7%)

Question 3

How is gluten an antigen?

Answer 3

• Gliadins and glutenins are rich in proline and glutamine amino acids
• Therefore resistant to proteolytic degradation by digestive enzymes
• TG2 deamidates glutamine to glutamic acid - bind to HLA-DQ2 on APCs

Question 4

What are HLA-DQ2 and HLA-DQ8?

Answer 4

• Class II MHC molecules expressed on surface of APCs
• Present in some people whi never develop coeliac disease - presence of genes necessary but not sufficient for disease development

Question 5

Describe pathophysiology of coeliac disease.

Answer 5

• Gliadin passes through intestinal epithelial layer
• Binds to HLA DQ2 or DQ8 - activates mucosal T cells
• Causes immune response - chronic inflammation of small bowel - epithelium damaged leading to malabsorption

Question 6

Describe the adaptive immune response in coeliac disease. PART 1

Answer 6

• Gluten enters lamina propria and deamidated by TG2
• Taken up by dendritic cells and presented on HLA-DQ2/8
• Gluten specific CD4+ T cells recognise and bind to gluten

Question 7

Describe the adaptive immune response in coeliac disease. PART 2

Answer 7

• CD4+ T cells secrete inflammatory cytokines causing tissue damage
• Gluten/TG2-specific B cells are activated
• B cells differentiate into plasma cells - antibodies secreted against gluten and TG2

Question 8

Describe epithelial cell destruction in coeliac disease.

Answer 8

• CD4+ T cells secrete inflammatory cytokines
• Inhibit regulatory CD4+ Treg cells - suppresses self-tolerance
• Activates intestinal IELs - target and kill stressed intestinal epithelial cells - VILLOUS ATROPHY

Question 9

What are the clinical signs and symptoms of coeliac disease?

Answer 9

• Failure to thrive (stunted growth, growth chart faltering)
• Chronic diarrhoea
• Constipation (coeliac disease should be considered whenever diagnosing idiopathic constipation)
• Abdominal bloating
• Irritability
• Features of anaemia (adolescents)
• Nausea and vomiting

Question 9

Name some features of villous atrophy.

Answer 9

• Loss of villi - flattened epitheloum
• Inflammatory cells infiltrate
• Increased number of IELs

Question 10

Describe dermatitis herpetiformis.

Answer 10

• Extraintestinal manifestations
• Red and raised patches with blisters that burst with scratching
• Common on elbows, knees, buttocks and scalp

Question 11

List some complications of coeliac disease

Answer 11

• Hyposplenism (anatomical or functional)
• Iron deficiency anaemia
• Malnutrition
• Osteoporosis
• Small bowel T-cell lymphoma
• Vitamin B12 and folate deficiency

Question 12

What are the 4 key changes seen on duodenal biopsies in those with coeliac disease?

Answer 12

• Presence of villous atrophy leading to a flat mucosa
• Crypt cell hyperplasia
• Intraepithelial cell lymphocytosis
• Inflammatory cell infiltration of the lamina propria

Question 13

What laboratory investigations can be done with someone suspected to have coeliac disease?

Answer 13

• Anti-tissue transglutaminase (tTG) antibodies and total IgA count
• IgG endomysial antibodies (EMA), IgG deamidated gliadin peptide (DGP) or IgG tTG
• Genetic HLA DQ2 and DQ8 screen

Question 14

What is the main treatment for coeliac disease?

Answer 14

LIFELONG GLUTEN FREE DIET

Question 15

What other laboratory abnormalities can come up that could potentially suggest coeliac disease?

Answer 15

• Iron-deficiency anemia in children
• Folate-deficiency anemia in adults
• Low albumin, calcium, potassium, and sodium
• Elevated alkaline phosphatase and prothrombin time