the prospective study and the new espghan protocol l. greco, d. mičetić-turk mediterranean network...

The prospective study and the

new ESPGHAN protocol

L. Greco, D. Mičetić-Turk

Mediterranean Network for Celiac Disease

Istanbul, June 30th 2012

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.

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

• 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

Children and adolescents with otherwise unexplained symptoms and signs of:

• 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

Asymptomatic children and adolescents with increased risk for CD:

Down syndrome

Turner syndrome

Dermatitis herpetiformis

Dental enamel defects

What is the optimal approach for MEDICEL prospective study?

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 ofduodenal 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 microsystems

simultaneus

multiple Ab test

IgA determination

HLA-DQ2/DQ8 status

New diagnostic tests

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

MEDICEL – prospective study

Background

• CD is a prevalent and curable condition affecting CD is a prevalent and curable condition affecting 1% of the population1% of the population

• The occurence of coeliac disease is The occurence of coeliac disease is increasing over timeincreasing over time

• CD is more prevalent than clinically detectedCD is more prevalent than clinically detected

• Prevalence among family members ~ 10%Prevalence among family members ~ 10%

Aims• To investigate the incidence of CD To investigate the incidence of CD

• To evaluate characteristics and severity of symptomsTo evaluate characteristics and severity of symptoms

• To estimate CD risk by HLA-SNPs determination in first To estimate CD risk by HLA-SNPs determination in first degree relativesdegree relatives

• To evaluate whether in cases with positive serological and To evaluate whether in cases with positive serological and genetic markers and with clinical symptoms the omission genetic markers and with clinical symptoms the omission of biopsies is possible in Mediterranean countries?of biopsies is possible in Mediterranean countries?

• Other??Other??

Study design

Prospective multicenter observation study in Prospective multicenter observation study in persons, who will be diagnosed based on:persons, who will be diagnosed based on:

- S- Standarized symptom assessment -tandarized symptom assessment -Physical examination -Physical examination -Serology – rapid test or more extensive Serology – rapid test or more extensive serology -serology -HLA testing -HLA testing -HistologyHistology

• Conditions for participation: - Conditions for participation: - To recruit at least 50-100 patients -To recruit at least 50-100 patients -Ethical Ethical approvalapproval by by the local ethical committeethe local ethical committee

Methods

Standarized questionnaire on:Standarized questionnaire on:

• family historyfamily history

• clinical symptomsclinical symptoms

• and CD related diseasesand CD related diseases

• malignances?malignances?

Methods

• Blood sampling for serology - central lab / local Blood sampling for serology - central lab / local lablab

• 2-5ml blood for TG2, DGP, EMA2-5ml blood for TG2, DGP, EMA

• Rapid tTG testRapid tTG test

• DNA samplingDNA sampling

• 2-3ml EDTA blood frozen as total blood (HLA 2-3ml EDTA blood frozen as total blood (HLA DQDQ22/DQ/DQ88 , non-HLA genes) , non-HLA genes)

• Saliva samplingSaliva sampling

Methods

• Histology – at least 5 biopsies from duodenum (4 Histology – at least 5 biopsies from duodenum (4 from 2from 2ndnd and 3 and 3rdrd part and 1 from the bulb) - part and 1 from the bulb) -Marsh criteriaMarsh criteria

• Statistical analysisStatistical analysis

• Financial calculationFinancial calculation

Participating clinical centresParticipating clinical centres

Sampling and deliverySampling and delivery

Central / local labCentral / local lab

Data safety

Every particiapting centre should treat the Every particiapting centre should treat the patient’s data confidentially.patient’s data confidentially.

Data analysis -data will be sent encoded to Data analysis -data will be sent encoded to coordinator – Prof Luigi Greco coordinator – Prof Luigi Greco

“Working with the web-database andBiobanking”

MEDICEL meeting 2011Bologna. April 5 2011

Jose Ramon Bilbao

The MediCel database… a newborn projecthttp//medicel.sedyne.org

type your name


This is an anonymous databaseSamples are coded: country_XXThis is an anonymous databaseSamples are coded: country_XX

This will be important for follow-up…This will be important for follow-up…

You should have your code safe with youcountry_XX = patient ID

You should have your code safe with youcountry_XX = patient ID


All fields are (*) compulsory!All fields are (*) compulsory!

is age at Dx enough?is age at Dx enough?

…but are they necessary?…but are they necessary?

…will checkProvide HLA testingProvide HLA testing

SNP-basedDQ2.5DQ2.2DQ8


other genetic studies?other genetic studies?

Provide affordableHLA testing

Provide affordableHLA testing




symptoms/signssymptoms/signs

are we happy?are we happy?

Benefits of the study

• For individuals – diagnosisFor individuals – diagnosis

• For MEDICEL partnersFor MEDICEL partners

─ New knowledge on local levelNew knowledge on local level

• For MEDICEL projectFor MEDICEL project

─ New knowledge – epidemiology of CD in New knowledge – epidemiology of CD in mediterannean countriesmediterannean countries

─ New knowledge – clinical pictureNew knowledge – clinical picture

─ New knowledge – genetics (non-HLA genes)New knowledge – genetics (non-HLA genes)

• Evaluation of new ESPGHAN protocolEvaluation of new ESPGHAN protocol

the prospective study and the new espghan protocol l. greco, d. mičetić-turk mediterranean network...

Documents

cd slide

cd risk

time cd

detected cd

population cd

incidence of cd

cd specific antibody

hlasnps determination