1. The prospective study and the new ESPGHAN protocol
L. Greco, D. Mičetić-Turk
Mediterranean Network for Celiac Disease
Istanbul, June 30th 2012 1 1 1 1

5. New recommendations The histology might be omitted in symptomatic cases, who have: - high IgA anti-tTG titres (above 10x upper normal limit), - verified by EMA positivity, - HLA DQ2 and/or DQ8 heterodimer positive.

6. Who should be tested for CD?
Children and adolescents with the otherwise unexplained symptoms and signs
Asymptomatic children and adolescents with increased risk for CD 6 6

7. Children and adolescents with otherwise unexplained symptoms and signs of:
chronic or intermittent diarrhoea
failure to thrive
weight loss
stunted growth
delayed puberty
amenorrhoea
iron-deficiency anaemia
nausea or vomiting
chronic abdominal pain
cramping or distension
chronic constipation
chronic fatigue
recurrent aphthous stomatitis (mouth ulcers)
dermatitis herpetiformis-like rash
fracture with inadequate traumas / osteopenia / osteoporosis
abnormal liver biochemistry 7 7

8. Asymptomatic children and adolescents with increased risk for CD:
type 1 diabetes mellitus
autoimmune thyroid disease
autoimmune liver disease
Down’s syndrome
Turner syndrome
Williams’ syndrome
selective IgA deficiency
1st degree relatives with CD
dermatitis herpetiformis 8 8

9. Dermatitis herpetiformis
Down syndrome
Dermatitis herpetiformis
Dental enamel defects
Turner syndrome 9

10. What is the optimal approach for MEDICEL prospective study?10 10 10

11. Diagnosis of CD history physical examination diagnostic tools:
CD specific antibody tests:
Anti-TG2, anti-DGP, EMA
HLA testing for DQ2 and DQ8
histological analysis of duodenal biopsies 11 11 11 11 11

12. If you suspect it - you will detect it
Diagnosis of CD
If you suspect it - you will detect it 12 12 12 12

13. New diagnostic tests serological tests
tissue transglutaminase Ab (t-TG)‏
reliable, relatively inexpensive test
rapid finger-prick t-TG test 13 13

14. New diagnostic tests new microsystems simultaneus multiple Ab test
IgA determination
HLA-DQ2/DQ8 status
Prince HE. Evaluation of the INOVA diagnostics enzyme-linked immunosorbent assay kits for measuring serum immunoglobulin G (IgG) and IgA to deamidated gliadin peptides. Clin Vaccine Imunol 2006.
Aleanzi M, et al. Celiac disease: antibody recognition against native and selectively deamidated gliadin peptides. Clin Chem. 2001 14 14

15. MEDICEL – prospective study Background
CD is a prevalent and curable condition affecting 1% of the population
The occurence of coeliac disease is increasing over time
CD is more prevalent than clinically detected
Prevalence among family members ~ 10% 15 15 15 15

16. Aims To investigate the incidence of CD
To evaluate characteristics and severity of symptoms
To estimate CD risk by HLA-SNPs determination in first degree relatives
To evaluate whether in cases with positive serological and genetic markers and with clinical symptoms the omission of biopsies is possible in Mediterranean countries?
Other?? 16 16 16 16

17. Study design
Prospective multicenter observation study in persons, who will be diagnosed based on:
- Standarized symptom assessment Physical examination Serology – rapid test or more extensive serology HLA testing Histology
Conditions for participation: To recruit at least patients Ethical approval by the local ethical committee 17 17 17 17

18. Standarized questionnaire on:
Methods
Standarized questionnaire on:
family history
clinical symptoms
and CD related diseases
malignances? 18 18 18 18

19. Methods Blood sampling for serology - central lab / local lab
2-5ml blood for TG2, DGP, EMA
Rapid tTG test
DNA sampling
2-3ml EDTA blood frozen as total blood (HLA DQ2/DQ8 , non-HLA genes)‏
Saliva sampling 19 19 19 19

20. Methods
Histology – at least 5 biopsies from duodenum (4 from 2nd and 3rd part and 1 from the bulb) - Marsh criteria
Statistical analysis
Financial calculation
Participating clinical centres
Sampling and delivery
Central / local lab 20 20 20 20

21. Data safety
Every particiapting centre should treat the patient’s data confidentially.
Data analysis -data will be sent encoded to coordinator – Prof Luigi Greco 21 21 21 21

22. “Working with the web-database and
Biobanking”
MEDICEL meeting 2011
Bologna. April
Jose Ramon Bilbao

23. The MediCel database… a newborn project
http//medicel.sedyne.org
type your name

24. This will be important for follow-up…
The MediCel database… a newborn project
http//medicel.sedyne.org
This is an anonymous database
Samples are coded: country_XX
You should have your code safe with you
country_XX = patient ID
This will be important for follow-up…

25. The MediCel database… a newborn project
http//medicel.sedyne.org

26. All fields are (*) compulsory!
The MediCel database… a newborn project
http//medicel.sedyne.org
SNP-based
DQ2.5
DQ2.2
DQ8
Provide affordable
HLA testing
All fields are (*) compulsory!
…but are they necessary?
is age at Dx enough?
…will check
Provide HLA testing
other genetic studies?
SNP-based
DQ2.5
DQ2.2
DQ8

27. The MediCel database… a newborn project
http//medicel.sedyne.org
symptoms/signs
are we happy?

28. The MediCel database… a newborn project
http//medicel.sedyne.org
symptoms/signs
are we happy?

29. Benefits of the study For individuals – diagnosis For MEDICEL partners
New knowledge on local level
For MEDICEL project
New knowledge – epidemiology of CD in mediterannean countries
New knowledge – clinical picture
New knowledge – genetics (non-HLA genes)‏
Evaluation of new ESPGHAN protocol 29 29 29 29