Immuno: Malabsorption CPC Pt.2 Flashcards
Describe the T cell response to gluten in coeliac disease.
- Peptides from gluten (gliadin) are deamidated by tissue transglutaminase
- Deaminated gliadin is taken up by antigen-presenting cells and presented to CD4+ T cells via HLA DQ2 or DQ8
- CD4+ T cell activation results in secretion of IFN-gamma and may increase IL-15 secretion
- These cytokines promote activation of intra-epithelial lymphocytes (gamma-delta T cells)
- The intraepithelial lymphocytes will kill epithelial cells via the NKG2D receptor (normally recognises the stress protein MICA)
Describe the B cell response to gluten in coeliac disease.
- B cells will process gluten antigens and present it to CD4+ T cells
- CD4+ T cells activated these B-cells whose surface receptors recognise gliadin
- These B-cells become plasma cells that secrete anti-gliadin antibodies
- These CD4+ T cells can also active B-cells whose surface receptors recognise tTg as part of the tTg/gliadin complex
- These B-cells then become plasma cells that secrete anti-tTg antibodies
What are the 2 most sensitive and specific antibodies used to test for coeliac disease?
- Anti-tTg antibodies
- Anti-endomysial antibodies
Anti-gliadin antibodies are not very sensitive nor specific
What important test should be performed before checking anti-tTg and anti-endomysial antibody levels?
IgA levels - IgA deficiency can produce false-negative results
Should you do endoscopy with duodenal biopsy even if coeliac serology is positive?
Yes - need to confirm diagnosis & take histological baseline
What are the characteristic histological features of coeliac disease?
- Villous atrophy
- Crypt hyperplasia
- Intra-epithelial lymphocytes (>25 lymphocytes per 100 epithelial cells)
Describe the villous atrophy seen in coeliac disease.
- Normal villous: crypt ratio is about 4: 1
- In coeliac disease, villous height is reduced and crypts become hyperplastic
- This leads to a reduced or reversed villous: crypt ratio
- The mucosa remains the same thickness due to crypt hyperplasia
- However, decreased surface area (due to villous atrophy) leads to malabsorption
List some other causes of villous atrophy.
Don’t learn - just know there are many causes
- Giardiasis
- Tropical sprue - v.rare
- Crohn’s disease
- Radiation/chemotherapy
- Nutritional deficiencies
- Graft-versus-host disease
- Microvillous inclusion disease
- Common variable immunodeficiency
List some other causes of high intraepithelial lymphocytes.
Don’t learn - just know there are many causes
- Dematitis herpetiformis
- Giardiasis
- Cows’ milk protein sensitivity
- IgA deficiency
- Tropical sprue
- Post-infective malabsorption
- Drugs (NSAIDs)
- Lymphoma
What does the interpretation of the histological report in suspected coeliac disease depend on?
Dietary history
(e.g. if the patient has been avoiding gluten then they may have normal histology)
How is coeliac disease managed?
Strict adherence to a gluten-free diet
Avoid: wheat, barley, rye, oats
Support: coeliac society, dieticians, family
List some complications of coeliac disease.
- Malabsorption
- Osteomalacia and osteoporosis
- Neurological disease (epilepsy and cerebral calcification)
- Lymphoma (EATL)
- Hyposplenism
What does a high anti-tTg antibody level in a patient with previously diagnosed coeliac disease suggest?
- Poor adherence with the diet
- Complications (e.g. small bowel lymphoma)
Describe the follow up investigation used for patient with coeliac
How often should a DEXA scan be performed in coeliac patients?
DEXA of spine and hip every 3-5 years
Describe the diagnostic workup for coeliac
