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Coeliac Disease -
Coeliac Pathogenesis
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Written by Dr Sebastian Zeki
MCQs for this page
Coeliac Pathogenesis
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Coeliac disease aetiology theories:
Genetic (10-15% have first degree relative with it).
Viral -
adenovirus
type 12 more common in coeliac.
Alpha
gliadin
has amino acid homologous to the
54KDa E1b protein coat of
adenovirus
12 so molecular mimicry is implicated.
B
r
e
a
k
d
o
w
n
i
n
g
u
t
TTG secreted by
fibroblasts and
inflammatory cells in
lamina propria
TTG
Glutamine containing
peptides
Glutamic acid
Deamidation
Because it is
negatively charged
it can bind to
HLA DQ2
Pro-inflammatory T cell
activation
+
G
l
u
t
e
n
Glutenin
Gliadin
Wheat
Rye
Barley
Hordein
Secalin
Secalin,
gliadin,
avenin and hordein
are collectively called
prolamins (soluble in
ethanol) and have
similar amino acid
residues. Avenin is
less toxic and oats
may be safe
Oats
Avenin
Specific
peptide
motifs as
yet not
specifically
isolated
Cellular
immunity
Humoral
immunity
The role of antibodies in disease
pathogenesis
Antigliadin antibodies are not essential for the pathogenesis of
coeliac disease.
IgA endomysial antibodies are rarely found without coeliac-
however CD patients without dont differ to those with the
antibodies.
Antibodies against TT may be of some pathogenic importance.
CD patients also have serum antibodies against other food proteins
such as beta-lactoglobulin, casein, and ovalbumin- reason unclear.
Genetic factors:
It is associated withHLA-DQ2 and/or DQ8 gene locus.
- HLA contribution to the development of celiac disease among siblings is 36 %.
Homozygosity for HLA DQ2 has been associated with an increased risk for refractory coeliac disease and enteropathy-
associated T-cell lymphoma .
It is associated with chromosome 15q26, which contains a type I diabetes susceptibility locus.
It is associated with chromosome 5q and possibly 11q.
It is associated with an unidentified gene on chromosome 6p.
There is a weak link with variants of the myosin IXB gene (MYO9B) located on chromosome 19 which hasbeen associated with
impaired intestinal barrier function and linked to coeliac disease, refractory celiac disease and
enteropathy
associated T-cell
lymphoma .
Epidemiology
It occurs primarily in whites of northern European ancestry.
Punjabis and Gujaratis from India who lived in England developed this disorder 2.7
times as frequently as Europeans when on a gluten-rich diet.
The prevalence of CD is around 1:184
In the at-risk groups, the prevalence is 1:22 in 1st-degree relatives and 1:39 in
2nd-degree relatives.
Pathogenesis of Coeliac Disease
Endosperm
Embryo
Bran
Written by Dr Sebastian Zeki
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