Coeliac Disease Flashcards
Which HLA predispose to coeliac disease?
HLA-DQ2
HLA-DQ8
Present in ~99% of patients
Where do enterocytes regenerate from?
SCs in the crypts of Lieberkuhn
What are the 3 histological features seen in advanced coeliac disease?
Intraepithelial lymphocytosis
Crypt hyperplasia (with increased mitosis)
Total villous atrophy
Describe the staging of coeliac disease
Type I: infiltrative (IELs)
Type II: hyperplastic (+ crypt hyperplasia)
Type II: destructive (+ villous atrophy)
List 5 other causes of IEL and villous atrophy with crypt hyperplasia
Tropical sprue Small bowel bacterial overgrowth Common variable immunodeficiency AI enteropathy Certain drugs
Describe the clinical presentation of coeliac disease
GI symptoms (diarrhoea, bloating, abdominal cramps, flatulence) IDA Vitamin deficiencies Nutrient malabsorption Osteoporosis Increased prevalence of AI diseases
What are some environmental influences on coeliac disease risk?
Protective: breast feeding
Risk: infections e.g. gastroenteritis, early or excessive introduction of gluten
Describe the pathogenesis of coeliac disease
Gliadins escape the action of GI proteases
Deamidated by tissue transglutaminase (tTG), converting glutamine residues to -ively charged glutamate
Deamidated gliadin is presented by APCs to CD4+ T cells (binds more efficiently to HLA-DQ2 and HLA-DQ8)
Cytokines are released, results in inflammatory response with activation of T cells and plasma cells
Plasma cells produced anti-tTG and anti-gliadin Abs
T cells express NKR and mediate cytotoxic immune response
How is coeliac disease diagnosed?
Serology for anti-tTG and deamidated gliadin peptide Abs (DPG-IgG)
HLA-DQ haplotyping (no DQ2 or DQ8 effectively rules out)
Gold standard is small bowel biopsy during gluten exposure
What are some of the possible long term sequelae of coeliac disease?
Enteropathy-associated T-cell lymphoma (EATL)
Small bowel adenocarcinoma
Oesophageal cancer
What type of hypersensitivity is coeliac disease?
IV (delayed type)
