Potential Celiac Disease (CD) in Chilcdren withCD Family Risk: Clinical Correlates and Outcome

Item Type Poster/Presentation

Authors Catassi, C. (Carlo); Lionetti, Elena; Castellaneta, Stefania;Pulvirenti, Alfredo; Tonutti, Elio; Francavilla, Ruggiero; Fasano,Alessio; The Italian working group on weaning and CD risk(SIGENP)

Publication Date 2012

Keywords Celiac Disease; Glutens--adverse effects; Autoimmune Diseases;Infant

Download date 13/01/2022 10:47:09

Item License https://creativecommons.org/licenses/by-nc-nd/4.0/

Link to Item http://hdl.handle.net/10713/2904

Potential Celiac Disease (CD) in children with CD

Family Risk:

Clinical Correlates and Outcome

Carlo Catassi,1,2 Elena Lionetti,3 Stefania Castellaneta,4 Alfredo Pulvirenti,5 Elio Tonutti,6 Ruggiero

Francavilla,7 Alessio Fasano,1

and “the Italian Working Group of Weaning and CD risk”.

1Center for Celiac Research, University of Maryland, Baltimore MD (USA), 2Department of Pediatrics, Università Politecnica delle

Marche, Ancona, Italy, 3Department of Pediatrics, University of Catania, Italy, 4Department of Pediatrics, San Paolo Hospital, Bari,

Italy, 5Department of Clinical and Molecular Biomedicine, University of Catania, Italy, 6Department of Immunopathology and

Allergology, Udine Hospital, Udine, Italy, 7Department of Developmental Biomedicine, University of Bari, Italy,

Background

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1Fasano A and Catassi C, Gastroenterology 2001

2Tosco A, et al, Clin Gastr Hepatol 2011 3Simell S, et al, Am J Gastr 2007

4Simell S, et al. Scand J Gastroenterol 2005 5Liu E, et al. Clin Gastroenterol Hepatol 2003

1. “Potential” celiac disease (CD) is characterized by a serum celiac-type antibody

response associated with a normal or minimally abnormal intestinal mucosa at

the biopsy.1

2. The destiny of potential CD is variable but may evolve into overt CD over time;2

3. However, in young children CD-related autoantibodies may disappear over time

without dietary treatment, suggesting the possibility of a fluctuating CD-type

response influenced by regulatory immune events.3-5

4. Identifying children that can reverse the autoimmune process may help

clarifying factors involved in either CD development or restoration of gluten

tolerance.

Aims of the study

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In a large cohort of children at family risk for CD participating in the Italian

Baby Study on “Weaning and CD risk” we aimed to evaluate:

1)the frequency of potential CD;

2)the natural history of CD-related antibodies in children with potential CD

left on a normal diet;

3)any possible discriminating factors between children with potential or

overt CD.

Infants at family risk for CD Enrolment from 2003 to 2009 in 20 Italian centers

4th – 6th

month

12th

month

AGA, EMA, and TTG at 24 and 36 months

and 5 years

HLA-DQ2/DQ8 + IgA tot

AGA, EMA and TTG at 15

months

12 months:

diet with gluten

Gluten

introduction

at 12 months

Gluten

introduction

at 4-6 months

Group A Group B

The Italian Baby-Study on Weaning and CD Risk

GFD

from 0 to 4 – 6

months

Positive for serology:

a) TTG > 20 U.I. and EMA pos;

b) AGA IgG in IgA deficit;

c) AGA IgA and IgG in <2 yrs

Patients and Methods

1. The study-group included Italian children participating in the Italian Baby Study on

“Weaning and CD risk”, and fulfilling the criteria for the small intestinal biopsy.

2. Diagnosis of CD was made in children with a CD-compatible HLA genotype, a Marsh-

Oberhuber 0-1 (potential CD) or 2-3 (overt CD) lesion at the biopsy, and one of the

following: 1) IgA tTG and EMA positivity; 2) AGA IgG positivity associated with IgA

deficiency; 3) AGA IgA positivity in children aged less than two years with clinical suspicion

of CD.

3. Potential CD children were followed-up and CD-related antibodies were determined every 6

months for 2 years. In patients with persistent antibody-positivity and/or symptoms after 2

years biopsies were repeated.

4. The following attributes were evaluated: age, sex, relative/s with CD, anti-

transglutaminase titre, HLA alleles, age at gluten introduction, and duration of

breastfeeding.

5. To investigated the presence of attributes with predictive power for potential CD vs overt

CD we trained a decision tree based on the C4.5 algorithm.

Results

1. Frequency of potential CD

75%

25%

Overt CD (72)

Potential CD (24)

101 positives (5 refused biopsy)

Potential CD-children (n=24) F 13 (50%); median age 2.1 years (range 1-5) 14 Marsh 0, 10 Marsh 1 23 TTG and EMA pos (1 AGA IgG pos) All asymptomatic Normal nutritional parameters No other autoimmune diseases

2. Natural history of 24 children with potential CD

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Risultati

24 potential CD

TTG + EMA+ n=23

TTG-, EMA – AGA IgG + (IgA deficiency)

n=1

gluten-free diet n=3

gluten-containing diet n=20

gluten-containing diet n=1

TTG EMA negative n=16

TTG EMA positive

n=2

TTG EMA fluctuating

n=2

AGA IgG negative

n=1

Villous atrophy

After 1 year

TTG EMA negative n=17

TTG EMA positive

n=1

TTG EMA fluctuating

n=2

AGA IgG negative

n=1

After 2 years

Overall:

86% negative

5% CD

9% fluctuating

Results

3. Anti-tTG values of the 21 potential CD-children continuing gluten-consumption at each time of follow-up

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4. Factors associated with potential CD versus overt CD

Precision 88.5% Sensitivity 0.93 Specificity 0.76

Results: decision-tree

Conclusions

1. The frequency of potential CD is high in at-risk infants, however the percentage of

spontaneous disappearance of CD-related antibodies is about 86% (at 2 years

from the first positivity).

2. Our study shows that in asymptomatic antibody-positive children with TTG levels

< 11 folds the decision of performing the biopsy should be preceded by a period

of repeated serological testing.

3. Breastfeeding may have a preventive role on future development of CD.

4. A prolonged follow-up of this cohort will clarify whether these children will develop

CD later in life.

Thanks to

Study-coordinator group

Carlo Catassi (Ancona)

Elena Lionetti (Catania)

Stefania Castellaneta (Bari)

Ruggiero Francavilla (Bari)

Associazione Italiana Celiachia

Adriano Pucci

Elisabetta Tosi

HLA typing

Bionat (Palermo)

Sandro Drago

Giovanni Maggiore

Alessandro Raffa

Serologycal testing

Menarini diagnostics (Firenze)

Massimo Donnini (Firenze)

Elio Tonutti (Udine)

The Italian working group on weaning and CD risk (SIGENP)

Sergio Amarri (Reggio Emilia)

Maria Barbato, Giulia Maiella, Ilaria Celletti (Roma)

Cristiana Barbera, Maria Kuvidi (Torino)

Graziano Barera, Giulia Tronconi (Milano)

Antonella Bellantoni (Reggio Calabria)

Emanuela Castellano (Genova)

Giuseppe Castellucci (Foligno)

Carlo Catassi, Francesca Aniballi, Simona Gatti (Ancona)

Maurizio Corvo (Milano)

Ruggiero Francavilla, Stefania Castellaneta (Bari)

Graziella Guariso (Padova)

Giuseppe Iacono (Palermo)

Elena Lionetti (Catania)

Giuseppe Lombardi (Pescara)

Giuseppe Magazzù, Donatella Sindoni (Messina)

Carlo Polloni (Rovereto)

Marinella Scotta (Varese)

Riccardo Troncone, Giovanna Limongelli (Napoli)

Giovanna Zuin (Milano)

Claudio Ughi (Pisa)

Statistical analysis

Alfredo Pulvirenti (Catania)