Celiac disease (CD) is a chronic intestinal inflammation caused by gluten ingestion in genetically predisposed individuals. Overt-CD and potential-CD are the two main forms of gluten intolerance in pediatric patients with different grades of intestinal mucosa lesion and clinical management. For overt-CD patients the gluten-free diet is mandatory, while for potential-CD the dietary therapy is recommended only for those subjects becoming clinically symptomatic overtime. To date, specific early biomarkers of evolution to villous atrophy in potential-CD are lacking. We recently observed an expansion of TCR??+ T cells and a concomitant disappearance of IL4-producing T cells in the intestinal mucosa of overt-CD patients compared to potential-CD children, suggesting the involvement of these two cells subsets in the transition from potential-CD to overt-CD. In this study, we demonstrated that the intestinal densities of IL4+ T cells inversely correlated with TCR??+ T cell expansion (p < 0.005) and with the serum levels of anti-tissue transglutaminase antibodies (p < 0.01). The changes of these two cell subsets strongly correlated with mucosal lesions, according to the histological Marsh classification, as the transition from M0 to M3 lesions was associated with a significant reduction of IL4+ T cells (M0 vs. M1 p < 0.04, M0 vs. M3 p < 0.007) and an increase of TCR??+ T cells (M0 vs. M1 p < 0.05, M0 vs. M3 p < 0.0006). These findings strongly suggest that the detection of TCR??+ and IL4+ T cells could serve as cellular biomarkers of mucosal lesion and targets of novel immunomodulatory therapies for CD.

Intestinal Cellular Biomarkers of Mucosal Lesion Progression in Pediatric Celiac Disease

Serena Vitale;Stefania Picascia;
2021

Abstract

Celiac disease (CD) is a chronic intestinal inflammation caused by gluten ingestion in genetically predisposed individuals. Overt-CD and potential-CD are the two main forms of gluten intolerance in pediatric patients with different grades of intestinal mucosa lesion and clinical management. For overt-CD patients the gluten-free diet is mandatory, while for potential-CD the dietary therapy is recommended only for those subjects becoming clinically symptomatic overtime. To date, specific early biomarkers of evolution to villous atrophy in potential-CD are lacking. We recently observed an expansion of TCR??+ T cells and a concomitant disappearance of IL4-producing T cells in the intestinal mucosa of overt-CD patients compared to potential-CD children, suggesting the involvement of these two cells subsets in the transition from potential-CD to overt-CD. In this study, we demonstrated that the intestinal densities of IL4+ T cells inversely correlated with TCR??+ T cell expansion (p < 0.005) and with the serum levels of anti-tissue transglutaminase antibodies (p < 0.01). The changes of these two cell subsets strongly correlated with mucosal lesions, according to the histological Marsh classification, as the transition from M0 to M3 lesions was associated with a significant reduction of IL4+ T cells (M0 vs. M1 p < 0.04, M0 vs. M3 p < 0.007) and an increase of TCR??+ T cells (M0 vs. M1 p < 0.05, M0 vs. M3 p < 0.0006). These findings strongly suggest that the detection of TCR??+ and IL4+ T cells could serve as cellular biomarkers of mucosal lesion and targets of novel immunomodulatory therapies for CD.
2021
Istituto di Biochimica e Biologia Cellulare - IBBC
IL4
TCR??+ T cells
biomarkers
pediatric celiac disease
translational research
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/447181
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