Celiac disease is an autoimmune disorder triggered by gluten that affects the small intestine and results in damage to the intestinal villi. It is estimated to affect at least 1% of the population. The only effective treatment is a lifelong gluten-free diet. Researchers are studying enzyme and drug therapies to allow ingestion of small amounts of gluten. Advances in diagnostic tests and screening tools may help reduce undiagnosed cases of celiac disease.

1. UNIVERSITY FERHATABBASSETIF 1
Facultyof natureand life sciences
DEPARTMENT OF BIOLOGY AND ANIMAL PHYSIOLOGY
Master 2 : Physiology and Pharmacology
Celiac disease
Presented by :
Moussa Hamza
Khames Habib
Mokhnache Djelal
Taleb Fawzi
Boukhalfa Zineddine
2015/2016

2. 2
Abstract:
Celiac Disease (CD) affects at least 1% of the population and evidence suggests
that prevalence is increasing [1]. Celiac disease is an autoimmune digestive
disease in which specific peptides from wheat, rye and barley (collectively
called gluten) trigger progressive destruction of the villi of the small intestine. In
those with a genetic predisposition and resolves with exclusion of gluten from
the diet [2]. The classic syndrome of celiac disease as originally described by
Gee [3]. Celiac disease can present with many symptoms, including typical
gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, fl
atulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g.,
abnormal liver function tests, iron deficiency anemia, bone disease, skin
disorders, and many other protean manifestations) [2]. Positive celiac serology,
characteristic histology and clinical improvement on gluten free diet are the
hallmarks for the diagnosis of celiac disease [4]. The treatment for celiac disease
is primarily a gluten-free diet.
With the better understanding of the pathogenesis, new targets have been
identified for the treatment of celiac disease.

3. 3
Pathophysiology
Through years of targeted research our knowledge and understanding of celiac
disease has accelerated. Clinical manifestations in patients affected with CD are
a result of complex interplay of environmental exposure, genetic predisposition,
and immunologic response [5].The gluten in wheat is composed of two proteins,
gliadins (the primary toxic component) and glutenins [5]. Gliadin, the alcohol-
soluble portion of gluten, cannot be fully broken down by the intestine, and
generally remains in the intestinal lumen of all individuals. In persons with
celiac disease, it can occasionally pass through the epithelial layer of the
intestine and stimulate an immune response [6] and cause enterocyte destruction
and subsequentvillous atrophy [5] (Fig. 1) in those with genetic susceptibility.
Normal villi Partial atrophy Total atrophy
Fig. 1: Enterocyte destruction and subsequent villous atrophy (Horvath K., 2002)
In these individuals, this poorly digested gliadin protein will bind to the human
leukocyte antigen class II DQ2 or DQ8 molecules, which then activates CD4 T
cells in the intestinal mucosa resulting in a cascade of inflammatory activation
and production of cytokines. Additionally, they secrete immunoglobulins,
cytokines, interferons, tumor necrosis factor, and interleukin 15 and 17. The
target of these autoantibodies is now known to be the enzyme tissue
transglutaminase (tTG). This enzyme may play a prominent role in the
pathogenesis of CD by deamidating gliadin, resulting in a greater proliferative
response of gliadin-specific T-cells [7]. This ultimately leads to tissue damage
(villous atrophy, crypt hyperplasia, and increased antibody-producing B cells).

4. 4
This autoimmune activation produces chronic inflammation of the proximal
small bowel intestinal mucosa, leading to malabsorption. (Fig. 2)
There may be environmental factors which play roles in the development of
celiac disease. There are some studies that indicate that infection may contribute
in the pathogenesis of celiac disease. Rod-shaped bacteria have been found in
small bowel biopsies of celiac children. Campylobacter enteric infection may
increase intestinal permeability in genetically predisposed individuals and thus
may increase the chance of developing celiac [4]
Fig. 2: Pathophysiology of celiac disease (Sollid and Lundin., 2009).
.

5. 5
Conclusion
Celiac disease is an inherited autoimmune disorder that affects the digestive
process ofthe small intestine.
When a person who has celiac disease consumes gluten, the immune system
responds by attacking the small intestine and inhibiting the absorption of
important nutrients into the body. Undiagnosed and untreated, celiac disease can
lead to the development of other autoimmune disorders, as well as osteoporosis,
infertility, neurological conditions, and, in rare cases, cancer.
At present, strict and lifelong gluten free diet is the only effective treatment for
celiac disease. Several drug treatments for celiac disease are under evaluation.
Researchers are also studying a combination of enzymes—proteins that aid
chemical reactions in the body—that detoxify gluten before it enters the small
intestine. Even small amounts of gluten can be immunogenic; therefore all food
and food items and drugs that contain gluten and its derivatives must be
eliminated completely from the diet. Advances in the utilization of diagnostic
tests and screening tools will help to reduce the number of undiagnosed patients.

6. 6
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