KINESIOL 1Y03 Chapter Notes - Chapter 11: Histology, Odds Ratio, Seroprevalence
22 Jun 2018
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Basics of coeliac disease
Defin: “ a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary
gluten in genetically susceptible individuals” Ludvigsson et al Gut 2012 / “gluten-sensitive
enteropathy”
N.B. the ESPGAN working group have classified the disease forms into new definitions including:
Classical, symptomatic, subclinical, asymptomatic, refractory (symptomatic + villous atrophy after
GFD for >12months), potential, gluten-related disorders
Clinical features
Frequent (>50%) = malaise, fatigue, steatorrhoea, diarrhoea, weight loss, anaemia, low folate, low
Fe
Common (>25%) = anorexia, abdo pain, oral ulcers, distension, bloating, flatulence, osteopenia,
childhood history, FH, low B12, low albumin, low 25-OH-bit D, high PTH
Occasional (<25%) = nausea, muscle cramps + tetany + bone pains (hypocalcaemia), bruising,
oedema, constipation, rashes, fractures, lymphoma, low Ca2+, low Mg2+, low Zn2+
- Some can be completely asymptomatic!
- Once thought to be a childhood disease, now know to present at any age
- Often diagnosed in the presence of Fe-deficiency anaemia, therefore commonly at >50yo, where
anaemia previously blamed on menstruation becomes cause for concern due to menopause.
Pathogenesis
- The active molecule is a 33-mer, specifically residues 57-89 of alpha-2-gliadin, which is stable in
digestive proteases.
- A glutamine aa is cross-linked by tTG and is deamidated to glutamate (= ‘DQ2--1 epitope’)
- This causes neo-antigen formation and stimulates HLA-restricted T cell clones from Coeliacs
– Shan et al. Science 2002
The immune response causes inflammatory damage and cell death (apoptosis) - Moss et al. Gut,
1996. Enterocyte apoptosis leads to villous atrophy and stimulated regeneration leads to
hyperplastic crypts.
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Defin: a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically susceptible individuals ludvigsson et al gut 2012 / gluten-sensitive enteropathy . N. b. the espgan working group have classified the disease forms into new definitions including: Classical, symptomatic, subclinical, asymptomatic, refractory (symptomatic + villous atrophy after. Frequent (>50%) = malaise, fatigue, steatorrhoea, diarrhoea, weight loss, anaemia, low folate, low. Common (>25%) = anorexia, abdo pain, oral ulcers, distension, bloating, flatulence, osteopenia, childhood history, fh, low b12, low albumin, low 25-oh-bit d, high pth. Occasional (<25%) = nausea, muscle cramps + tetany + bone pains (hypocalcaemia), bruising, oedema, constipation, rashes, fractures, lymphoma, low ca2+, low mg2+, low zn2+ Once thought to be a childhood disease, now know to present at any age. Often diagnosed in the presence of fe-deficiency anaemia, therefore commonly at >50yo, where anaemia previously blamed on menstruation becomes cause for concern due to menopause.
