The prospective study and the new ESPGHAN protocol

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

New recommendations The histology might be omitted in symptomatic cases, who have: - high Ig. A anti-t. TG titres (above 10 x upper normal limit), - verified by EMA positivity, - HLA DQ 2 and/or DQ 8 heterodimer positive.

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

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

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 Ig. A deficiency • 1 st degree relatives with CD • dermatitis herpetiformis

Dermatitis herpetiformis Dental enamel defects Down syndrome Turner syndrome

What is the optimal approach for MEDICEL prospective study?

Diagnosis of CD history physical examination diagnostic tools: • CD specific antibody tests: • Anti-TG 2, anti-DGP, EMA • HLA testing for DQ 2 and DQ 8 • histological analysis of duodenal biopsies

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

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

New diagnostic tests new microsystems simultaneus multiple Ab test Ig. A determination HLA-DQ 2/DQ 8 status Prince HE. Evaluation of the INOVA diagnostics enzyme-linked immunosorbent assay kits for measuring serum immunoglobulin G (Ig. G) and Ig. A 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

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%

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? ?

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 50 -100 patients Ethical approval by the local ethical committee -

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

Methods • Blood sampling for serology - central lab / local lab • 2 -5 ml blood for TG 2, DGP, EMA • Rapid t. TG test • DNA sampling • 2 -3 ml EDTA blood frozen as total blood (HLA DQ 2/DQ 8 , non-HLA genes) • Saliva sampling

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

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

“Working with the web-database and Biobanking” MEDICEL meeting 2011 Bologna. April 5 2011 Jose Ramon Bilbao

The Medi. Cel database… a newborn project http//medicel. sedyne. org type your name

The Medi. Cel 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…

The Medi. Cel database… a newborn project http//medicel. sedyne. org

The Medi. Cel database… a newborn project http//medicel. sedyne. org SNP-based DQ 2. 5 DQ 2. 2 DQ 8 Provide affordable testing All. HLA fields are (*) compulsory! …but are they necessary? SNP-based DQ 2. 5 DQ 2. 2 DQ 8 is age at Dx enough? …will check Provide HLA testing other genetic studies?

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

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

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