Recognizing the Emergent and Submerged Iceberg of the Celiac Disease: ITAMA Project-Global Strategy Protocol

Giuseppe Magazzù, Samuel Aquilina, Christopher Barbara, Ramon Bondin, Ignazio Brusca, Jacqueline Bugeja, Mark Camilleri, Donato Cascio, Stefano Costa, Chiara Cuzzupè, Annalise Duca, Maria Fregapane, Vito Gentile, Angele Giuliano, Alessia Grifò, Anne-Marie Grima, Antonio Ieni, Giada Li Calzi, Fabiana Maisano, Giuseppinella Melita, Socrate Pallio, Ilenia Panasiti, Salvatore Pellegrino, Claudio Romano, Salvatore Sorce, Marco Elio Tabacchi, Vincenzo Taormina, Domenico Tegolo, Andrea Tortora, Cesare Valenti, Cecil Vella, Giuseppe Raso, Giuseppe Magazzù, Samuel Aquilina, Christopher Barbara, Ramon Bondin, Ignazio Brusca, Jacqueline Bugeja, Mark Camilleri, Donato Cascio, Stefano Costa, Chiara Cuzzupè, Annalise Duca, Maria Fregapane, Vito Gentile, Angele Giuliano, Alessia Grifò, Anne-Marie Grima, Antonio Ieni, Giada Li Calzi, Fabiana Maisano, Giuseppinella Melita, Socrate Pallio, Ilenia Panasiti, Salvatore Pellegrino, Claudio Romano, Salvatore Sorce, Marco Elio Tabacchi, Vincenzo Taormina, Domenico Tegolo, Andrea Tortora, Cesare Valenti, Cecil Vella, Giuseppe Raso

Abstract

Coeliac disease (CD) is frequently underdiagnosed with a consequent heavy burden in terms of morbidity and health care costs. Diagnosis of CD is based on the evaluation of symptoms and anti-transglutaminase antibodies IgA (TGA-IgA) levels, with values above a tenfold increase being the basis of the biopsy-free diagnostic approach suggested by present guidelines. This study showcased the largest screening project for CD carried out to date in school children (n=20,000) aimed at assessing the diagnostic accuracy of minimally invasive finger prick point-of-care tests (POCT) which, combined with conventional celiac serology and the aid of an artificial intelligence-based system, may eliminate the need for intestinal biopsy. Moreover, this study delves deeper into the "coeliac iceberg" in an attempt to identify people with disorders who may benefit from a gluten-free diet, even in the absence of gastrointestinal symptoms, abnormal serology and histology. This was achieved by looking for TGA-IgA mucosal deposits in duodenal biopsy. This large European multidisciplinary health project paves the way to an improved quality of life for patients by reducing the costs for diagnosis due to delayed findings of CD and to offer business opportunities in terms of diagnostic tools and support.

Keywords: ESPGHAN; anti-transglutaminase; artificial intelligence; coeliac disease; guidelines; intestinal biopsy; mucosal deposits; negative predictive value; point-of-care test.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Diagram of study protocol in Malta, number of patients enrolled as of March 2022, and preliminary results.
Figure 2
Figure 2
Diagram of study protocol in the Digestive Endoscopy Unit Setting, number of patients enrolled as of March 2022, and expected results.
Figure 3
Figure 3
Study protocol in Sicily at the Celiac Center Setting, number of patients enrolled as of March 2022, and expected results.
Figure 4
Figure 4
In yellow, the overlap of green and red indicates the deposits of anti-tTG2 on confocal microscopy.
Figure 5
Figure 5
Deposition of IgA is shown in green, and deposition of TG2 is shown in red.

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