Oral Presentation International Celiac Disease Symposium 2026

CHILDREN WITH DOWN SYNDROME DISPLAY A DISTINCT INTESTINAL MUCOSAL PHENOTYPE BEYOND CELIAC DISEASE (144948)

Roberta Rotondo 1 2 , Francesca Furone 1 , Claudia Bellomo 1 2 , Giovanna Zuin 3 , Maria Antonia Maglio 1 2 , Merlin Nanayakkara 1 2 , Renata Auricchio 1 2 , Maria Vittoria Barone 1 2
  1. Department of Translational Medical Sciences, Section of Pediatrics , University of Naples Federico II, Naples, Italy
  2. European Laboratory for the Investigation of Food Induced Diseases (ELFID), Department of Translational Medical Science, Section of Pediatrics , University of Naples Federico II, Naples
  3. MBBM Foundation, Pediatric Department, Hospital San Gerardo, University of Milano Bicocca, Monza, Italy

Down Syndrome (DS) have a 6-10 times higher risk of developing Celiac Disease (CeD).The reason for this increased predisposition is not yet clear. Low-grade inflammation appears to be a common pathogenic factor in both diseases, underlying mucosal damage in CeD and contributing to Alzheimer’s disease in DS. The current literature suggests that the range of intestinal alterations in DS is broader than just increased CeD incidence.

Our aim was to study inflammation on intestinal biopsies and organoids from DS children with normal duodenal mucosa (DS) and celiac disease (DS-CeD) compared to controls (CTRs) and CeD and to evaluate the released cytokines.

Intestinal organoids and biopsies were collected from 3 DS, 5 DS-CeD, 5 CTRs and 5 CeD. Immunofluorescence and immuhistochemestry allowed to study markers of inflammation (CD25+ cells), immune response (TCRγdelta+ and CD3+ cells, anti-tissue-transglutaminase-IgA-deposits) and proliferation (%Ki67) on biopsies. Organoids both in presence and absence of gliadin peptides were tested for pNF-KB levels by Western Blot and their colture media for Cytokinome (Biomultiplex).

As expected, markers of inflammation, immune activation and proliferation were increased in DS-CeD similarly to CeD biopsies. Surprisingly DS biopsies presented inflammation, high crypt proliferation and positivity for anti-tTG deposits, in absence of intraepithelial lymphocytes.

Intestinal organoids, derived from DS, DS-CeD were inflamed with respect to controls, at similar levels of CeD organoids. Gliadin peptides increased pNF-kb in CeD and DS-CeD as well as DS. 6 out of 27 cytokines (IL-1, IL-8, GM-CSF, IFN-y, MCP-1, IP-10) were increased in DS supernatants, all related to the NF-κβ pathway.

In conclusion DS duodenal mucosa is inflamed and reactive to gluten even in the absence of atrophy. Our data imply that intestinal alterations of these children are present.  Future research will focus on investigating the role of diet, including gluten, with inflammation and cognitive deficit, typical of DS.

 

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