Potential Coeliac Disease. The Italian Baby-Study on Weaning and CD Risk. 15m 24m 36m Tot. 15m 24m 36m Tot. in a Large Cohort of at-risk Infants:

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1 Potential Coeliac Disease in a Large Cohort of at-risk Infants: The Italian Baby-Study on Weaning and Risk Veronica Albano Elena Lionetti, Carlo Catassi and The Italian Working Group on Weaning and Celiac Disease Risk University of Catania (Italy), Università Politecnica delle Marche, Ancona (Italy) and University of Maryland, Baltimore (USA) Background: potential coeliac disease 1. Potential coeliac disease () is defined as the positivity of coeliac-related antibodies,butanormal,orminimallyabnormal,mucosa; 1 2. Thenaturalhistoryofthisconditionisunclear; 2 15m 24m 36m Tot 3. Theneedtostartalife-longglutenfreedietisstilldebated; 2 4. Someauthorsrecordedaprogressiontovillousatrophylaterinlife; In at-risk children antibodies may disappear spontaneously even on a glutencontainingdiet. 5 1 Fasano A and Catassi C, Gastroenterology Di Sabatino A and Corazza GR; Lancet Kurppa K, et al; J Ped Tosco A, et al, Clin Gastr Hepatol Simell S, et al, Am J Gastr 2007 Aims of the study Inalargecohortofchildrenatfamilialincreasedriskofwewantedto: 1) evaluate the prevalence and the natural history of potential ; 15m 24m 36m Tot 2) identify factors associated with potential by using a data mining approach based on decision-tree induction. 1

2 we analyzed a cohort of children recruited in the Italian Baby Study on weaning and risk between the years that developed autoimmunity and met the criteria for the diagnosis of potential celiac disease. The Italian Baby-Study on Weaning and Risk 729 infants at familial risk of Enrolment from 2003 to 2009 in 20 Italian centers 4th 6th month Group A GFD from 0 to 4 6 months Group B Gluten introduction at 4-6 months Gluten introduction at 12 months 12th month 12 months: diet with gluten 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 HLA-DQ2/DQ8 + IgA tot AGA, EMA and TTG at 15 months AGA, EMA, and TTG at 24 and 36 months and 5 years Patients and Methods 1. All children with positive serology underwent a duodenal examination comprising: 4 distal biopsies and 1 bulb biopsy; 2. Adiagnosisofpotentialwasmade(Marsh0orMarsh1score),potential were selected and suggested to continue an unrestricted diet 3. Celiac-related antibodies were determined every 6 months for at least 2 years. In patients with persistent antibody-positivity after 2 years biopsies were repeated. 4. The following attributes were evaluated: age, sex, relative/s with, antitransglutaminase titre, HLA alleles, age at gluten introduction(group A or B), and duration of breastfeeding. 5. The data mining investigated the presence of attributes with predictive and discriminant power for potential vs. Decisional trees were developed by using the C 4.5 algorithm. 2

3 Results Percentage of 97 pos 3 AGA IgG pos in IgA deficit 1 AGA IgA pos (symptoms) 101 positives (5 refused biopsy), 96 had the procedure F 13 (50%); median age 2.1 years (range 1-5) 14Marsh0,10Marsh1 23TTGandEMApos(1a-DPGIgGpos) 25% All but one symptomless Normal nutritional parameters No other autoimmune diseases 75% MC (72) Marsh score 2-3 MC potenziale (24) Marsh score 0-1 All children with potential but one were -symptom free -showed significantly lower ttg antibody levels than those with overt. no significant differences were found between groups in terms of age, gender, familiarity, age at gluten introduction, nutritional characteristics and HLA status. Results 2 year outcome of children with potential 24 potential TTG + EMA+ 3 TTG-, EMA AGA IgG + (IgA deficiency) gluten-free diet n=3 gluten-containing diet 0 After 1 year gluten-containing diet negative AGA IgG 6 positive fluctuating negative After 2 years negative AGA IgG 7 positive fluctuating negative Villous atrophy 3

4 Results Follow-up of serology of 21 children (3 on GFD) TTG values Fluctuating values Persistent positivity Normal values Overall: 85.7% (18/21)negative 4.8%(1/21) 9.5%(2/21) fluctuating Symptoms at Variables evaluated: diagnosis Age Gender asymptomathic Relative with HLA Age at gluten introduction Typical or atypical Breastfeeding duration Anti-transglutaminase titers <11 x TTG level >11 x <24 months Age at diagnosis >24 months Potential <=4.5 x Breastfeeding duration >= 8 months TTG level <= 8 months >4.5 x Potential Conclusions 1. The high prevalence of potential (25%) in infants at family risk of with positive serological markers is a novel finding of this study. 2. In our series of 21 children with potential, the spontaneous loss of serum autoimmunity (anti-ttg and EMA antibodies) was the most frequent outcome occurring in 86% of cases. 3. Our study shows that in symptomless antibody-positive children with TTG levels < 11 folds the decision of performing the biopsy should be preceded by a period of repeated serological testing. 4. A path in the decision tree stresses how prolonged breastfeeding may have a preventive role on future development of. 5. A prolonged follow-up of this cohort will clarify whether these children will develop later in life. 4

5 Thanks to Study-coordinator group Carlo Catassi Elena Lionetti Stefania Castellaneta Ruggiero Francavilla Associazione Italiana Celiachia Adriano Pucci Elisabetta Tosi Serologycal testing Menarini diagnostics(firenze) Massimo Donnini(Firenze) Elio Tonutti(Udine) HLA typing Bionat(Palermo) Sandro Drago Giovanni Maggiore Alessandro Raffa Statistical analysis Alfredo Pulvirenti(Catania) The Italian working group on weaning and 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)...thank you for your attention!.addresses: - Elena Lionetti elenalionetti@inwind.it - Carlo Catassi catassi@tin.it 5