Coeliac Disease Flashcards
What is coeliac disease?
- Autoimmune disorder - characterised by gluten sensitivity
- Can be diagnosed at any age
- More prevalent in women
What are the risk factors for coeliac disease?
Genetics (around 70% if monozygotic twin affected)
Autoimmune thyroid disease (15%)
Dietary gluten
Type 1 diabetes mellitus (8%)
IgA deficiency (7%)
How is gluten an antigen?
- 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
What are HLA-DQ2 and HLA-DQ8?
- 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
Describe pathophysiology of coeliac disease.
- 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
Describe the adaptive immune response in coeliac disease. PART 1
- 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
Describe the adaptive immune response in coeliac disease. PART 2
- 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
Describe epithelial cell destruction in coeliac disease.
- 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
What are the clinical signs and symptoms of coeliac disease?
- 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
Name some features of villous atrophy.
- Loss of villi - flattened epitheloum
- Inflammatory cells infiltrate
- Increased number of IELs
Describe dermatitis herpetiformis.
- Extraintestinal manifestations
- Red and raised patches with blisters that burst with scratching
- Common on elbows, knees, buttocks and scalp
List some complications of coeliac disease
- Hyposplenism (anatomical or functional)
- Iron deficiency anaemia
- Malnutrition
- Osteoporosis
- Small bowel T-cell lymphoma
- Vitamin B12 and folate deficiency
What are the 4 key changes seen on duodenal biopsies in those with coeliac disease?
- Presence of villous atrophy leading to a flat mucosa
- Crypt cell hyperplasia
- Intraepithelial cell lymphocytosis
- Inflammatory cell infiltration of the lamina propria
What laboratory investigations can be done with someone suspected to have coeliac disease?
- 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
What is the main treatment for coeliac disease?
LIFELONG GLUTEN FREE DIET
What other laboratory abnormalities can come up that could potentially suggest coeliac disease?
- Iron-deficiency anemia in children
- Folate-deficiency anemia in adults
- Low albumin, calcium, potassium, and sodium
- Elevated alkaline phosphatase and prothrombin time
