Coeliac Disease Flashcards
What is a hallmark of coeliac disease?
remission on a gluten free diet
Where do you mainly find gluten?
wheat
barley
rye
Coeliac disease definition?
immunologically mediated disease in genetically susceptible people driven by gluten antigen
Prevalence of Coeliac disease?
1:100
Coeliac disease has strong association with which genes?
HLA-DQ2
HLA-DQ8
When does Coeliac disease manifest?
anytime from infancy to late adulthood
what’s the treatment for Coeliac disease?
gluten-free diet only
what mainly gets absorbed in the ileum?
Vitamin B12 and bile acids
what are valves of Kerkring?
found in duodenum
circumferential rings to increase surface area
how many cells (kgs) do we lose every 2-3 days ?
1kg
crypts produce how many cell per day?
200-300 cells and climb the villus
how are chylomicrons absorbed?
via lymphatics
what is the ratio for mature to crypt cells?
4:1
what are Paneth cells for?
secrete natural defensins (antibiotics) to ward off pathogens
What is IELs?
intraepethelial lymphocytes
how does the small bowel keep bacteria undercontrol overall?
by being in a constant state of controlled mild inflammation
normally how many CD3/CD8 cells per enterocytes?
<25/100
what do you see in advanced Coeliac disease histologically? 3 things
total villous atrophy
crypt hyperplasia
intraepithelial lymphocytosis
what is the ratio of IELs per enterocytes in Coeliac disease?
2-3 per enterocyte! More plasma cells
what do the microvilli in Coeliac disease look like?
distorted
stunted
What do you find in Marsh Type I?
more than 30 IELs per 100 enterocyte
What do you find in Marsh Type II?
elongation and branching of crypts
What do you find in Marsh Type III?
villi shortened and blunted
villous to crypt ratio is less than 1:4
In Marsh Type III what is there a marked increase in?
CD8 and T-cells
other causes of villous atrophy?
tropical sprue
other immunodeficiency
autoimmune enteropathy
drugs: mycophenolate mofetil (used in transplants)
Gastro clinical presentations of Coeliac disease?
fatty diarrhea bloating cramps flatulence malabsorption of nutrients
nutrients affected by Coeliac disease?
anaemia
vitamin deficiencies
bones and general disposition of Coeliac disease?
osteoporosis risk
lethargic
migraines
people with Coeliac disease have increased prevalence of what else?
autoimmune diseases
type I diabetes
thyroiditis
Coeliac disease in babies consequences?
failure to thrive
does Coeliac disease have to be symptomatic?
could be asymptomatic
age of many new Coeliac disease diagnosis?
0-9
30-59
4 elements in pathogenesis of Coeliac disease?
genetics
environment
T-cells
Gluten
what % of people have this gene in Coeliac disease?
99.6% have the HLA-DQ2/DQ8
how many people who have HLA-DQ2.DQ8 don’t have Coeliac disease?
20-30%
what does HLA-DQ2/DQ8 do?
helps with antigen presentation to T-Cells
infant environment for Coeliac disease is avoided how? 3 ways
breast feeding
timing of gluten introduction
prevention of infections
Where are the CD4 cells that react to gluten?
in the small bowel mucosa
how do CD4s cause damage in Coeliac disease?
IFN-y
how is the innate immune response in Coeliac disease?
CD8+ and NK cells accumulate in epethelium
What proteins from wheat are the culprits for Coeliac disease?
Gliadins (alcohol soluble)
Glutenins
What does proline do to toxic gluten peptides?
proline resists digestion by proteases and increases toxicity
so what? high glutamine and proline and resists digestion?
it allow to pass through intestinal epithelium intact
what happens after intact peptides pass through intestinal epithelium?
convert glutamine to negatively charged glutamate
what converts glutamine to negatively charged glutamate?
tTG
tissue transglutaminase
so big deal, there’s negatively charged glutamate?
they can bind to HLA-DQ2 T-cell receptor on an APC. effectively making the glutamate an antigen
what happens after peptides bound to receptor on APCs??
bound to MHCII and start making cytokines
what antibodies are made by plasma cells in Coeliac disease?
anti-tTG
anti AGA
how do the enterocytes apoptose?
gliadin activated perforins are released
can Coeliac disease give you cancer?
T-cell malignancy is possible
get autoreactive IEL
Serological dx of Coeliac disease?
tTG antibody
deaminated gliadin peptide ( DGP-IgG)
what is gold standard for dx of Coeliac disease?
small bowel biopsy during gluten exposure
how soon to get the diagnosis of Coeliac disease?
the earlier the better
long term risks are bad
long term risks of undiagnosed Coeliac disease?
osteoporosis
autoimmune diseases
cancer
