the prospective study and the new espghan protocol l. greco, d. mičetić-turk mediterranean network...
TRANSCRIPT
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:
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
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
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
The MediCel database… a newborn projecthttp//medicel.sedyne.org
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
SNP-basedDQ2.5DQ2.2DQ8
other genetic studies?other genetic studies?
Provide affordableHLA testing
Provide affordableHLA testing
SNP-basedDQ2.5DQ2.2DQ8
SNP-basedDQ2.5DQ2.2DQ8
The MediCel database… a newborn projecthttp//medicel.sedyne.org
symptoms/signssymptoms/signs
are we happy?are we happy?
The MediCel database… a newborn projecthttp//medicel.sedyne.org
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