CELIAC DISEASE

and
GLUTEN RELATED
DISORDERS
Grain
Gluten a gliadin
 Grains
Neolitic revolution
10.000 years ago ~ 300 generation

Grain breeding (tetra- or hexa-ploid)

Increased imunogenicity of grains

Historické změny diety

https://uheart.wordpress.com/2013/04/01/the-paleolithic-diet-pale-o-or-pale-no/
 „Inflammatory“ diet
Refined starches, carbohydrates
Saturated FA, trans-unsaturated FA
Lack of : antioxidants (fruit and vegetables)
wholegrain products
ω-3 unsaturated FA

Aktivation of immune system (innate)

 Changes
of intestinal immune system

„inflammatory“ diet and

overeating
mode of delivery
breastfeeding
overuse of ATB
lack of vitamin D
Sapone et al. BMC Medicine 2012;10:13.
Wheat allergy

Non-celiac
gluten sensitivity
 Celiakie
genetic background
+
autoantibodies
+
histological changes
of small intestine
 Celiac disease
- genetic component
HLA-DQ 2/8, non-HLA genes
- permanent sensitivity to gluten
- autoimunne enteropathy
and systemic disorder
- may appear in any age
 Development
of celiac disease
HLA DQ2/8 + GLUTEN
non-HLA genes
non-gluten content of grain
absence of breastfeading
infection (rotavirus, adenovirus12)
stress

CELIAC DISEASE
 HLA DQ2/8

whole population

HLA
DQ2/DQ8
35-40%

2-3% celiac disease

Pathophysiology of CD
Pathophysiology of CD
autoimunne enteropathy
= impairment of all small intestinal functions

Malabsorption
(makro- and/or mikro-nutrients)

Impairment of barrier a immune functions:

……extraintestinal signs and symptoms
Malabsorption: symptoms
 diarrhea /steatorea
 abdominal pain, bloating, constipation
 anorexia, vomiting
 failure to thrive or weight loss (short
stature)
 fatigue
 iron deficiency anemia
 osteoporosis
Impairment of barrier a
immune functions:
symptoms
associated autoimmune diseases
(?) malignancy
 Dermatology

 dermatitis herpetiformis Dühring

 alopecia areata
 psoriasis
Dermatitis herpetiformis
Duhring
Alopecia areata
Psoriasis
 Gastroenterology and
hepatology
 microscopic colitis
 autoimmune hepatitis
 primary biliary cirrhosis and
primary sclerosing cholangitis
 irritable bowel syndrome
 inflammatory bowel diseases
 Endocrinology

 type 1 diabetes mellitus

 autoimmune thyroiditis
 Addison disease
 osteoporosis
 Hematologie
 iron deficiency anemia
 non-Hodgkin lymphoma
 intestinal T-cell lymphoma
 Rheumatology
 arthritis, arthralgia
 Sjögren syndroma
 rheumatoid arthritis
 systemic lupus erythematosus
 others
 Immunology

 IgA deficiency
 atopic conditions
 Neurology
 gluten ataxia
 peripheral neuropathy

 multiple sclerosis

 myopathy of unknown origin

 myastenia gravis

 recurring headaches

 seizures
 Psychiatry
 anxiety
 panic attacks
 depression

.
 Gynecology and
sexuology
 delayed puberty
 amenorrhea, dysmenorrhea

 unexplained infertility

 miscarriage
 Stomatology

 dental enamel hypoplasia

 aphthous ulcers
 glossitis
 cheilosis
Chromosomal disorders

 Down syndrome
 Turner syndrome

 Williams syndrome
 Risk of untreated CD
 hidden malabsorption
 associated autoimmune disease
 malignancy:
T-cell intestinal lymphoma
non-Hodgkin lymphoma
adenocarcinomas
 Prevalence of CD

 worldwide
 Europe and USA 0,5-1%
 Diagnosis of CD
When consuming gluten ! :

antibodies
(TTG, DGP, EMA), total IgA

+
enterobiopsy
(vilous atrophy)
 In children:
„triple test“ ESPGHAN
avoiding intestinal biopsy

* typical symptoms
* HLA-DQ2/8
* anti-tTG more than 10x ULN
+ EMA positivity
(in another blood sample)
 Serology
 anti-gliadin antibodies (AGA),
 anti-endomysial antibodies
(AEA, EMA) IgA, IgG
 anti-tissue transglutaminase
(anti-tTG) IgA, IgG
 Anti-deaminaded gliadin
peptides (DGP) IgA, IgG
 Total IgA
Biopsy: 4-6
Histology – Marsh classification
Marsh 3c
 Genetic testing

 HLA DQ2, HLA DQ8

 diagnostic difficulties
 1.st degree relatives
 Skrining of CD
- 1st. degree relatives
- risk groups:
type 1 diabetes, autoimmune thyroiditis
dermatitis herpetiformis
autoimmune hepatitis, colon irritabile
osteoporosis
iron-deficiency anemia
infertility
neuropsychiatric abnormalities
 Treatment
Gluten free diet
< 20ppm - 20mg gluten/kg
? diary
? oats

Substitute: iron, zinc, calcium, vit D, B, …

Refractory celiac disease

 Non-celiac gluten sensitivity
(NCGS)
intestinal symptoms:
- bloating, flatulence (~72%)
- abdominal pain (68-77%)
- diarrhoea (38-40%)
- constipation (~18%)
- GE reflux (20%)
- chronic ulcerative stomatitis (10%)
Sapone et al. BMC Med 2012;10:13
Volta et al. J Clin Gastroenterol 2012;46: 680–685.
 Non-celiac gluten sensitivity
(NCGS)
extraintestinal symptoms:
- eczema, erytema (33-40%)
- headache (32-35%)
- chronic tiredness (33-36%)
- disturbances in attention (34-42%)
- depresion, anxiety (15-22%)
- numbnes of hands and feets (17-20%)
- aoint and muscle pain (11-28%)
- anemia (15%) Sapone et al. BMC Med 2012; 10:13
Volta et al. J Clin Gastroenterol 2012;46:680–685.
 NCGS – diagnosis

Diagnosis per exclusionem (vyloučení CD a WA)

negative immuno-alergy testing (skin test + Ab)
negative CD serology
normal small intestinal biopsy
+/- AGA IgG
disappering of symptoms after gluten withdrawal
gluten challenge

Sapone et al. BMC Medicine 2012, 10:13

NCGS - pathogenesis

Volta et al. Cellular & Molecular Immunology 2013; 10: 383–392.

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