IMMUNE DYSREGULATION AND EPITHELIAL STRESS IN CELIAC DISEASE PROGRESSION: A FOCUS ON REFRACTORY CELIAC DISEASE SUBTYPES.

BACKGROUND

Celiac disease (CD) is a chronic autoimmune disorder triggered by gluten, leading to immune-mediated injury in the small intestine. While many patients show improvement with a gluten-free diet (GFD), some progress to refractory celiac disease (RCD), a condition that is not responsive to GFD. The mechanisms behind RCD are poorly understood, particularly in distinguishing it from regular CD.

AIM OF STUDY: This study aims to explore the immunohistochemical profiles of CD and RCD, with a focus on immune dysregulation and epithelial stress markers.

MATERIAL AND

METHODS

We conducted a retrospective analysis of 93 patients with CD, including those in Marsh stages 1, 2, 3a, and 3b, as well as RCD subtypes (Type I and Type II). Tissue samples were examined for the expression of CD3, CD8, CD103, FOXP3, Ki-67, MHC I, and MHC II, and the results were compared across the groups.

RESULTS

The study revealed progressive immune activation and epithelial stress as disease severity increased. FOXP3-positive regulatory T cells decreased significantly in RCD, especially in Type II, indicating a loss of immunoregulatory control. Elevated Ki67 indices were observed in the more severe stages, indicating active regeneration of epithelial cells. MHC II expression was upregulated in advanced stages, particularly in RCD, indicating enhanced antigen presentation.

CONCLUSION

Our findings underscore the crucial role of immune dysregulation and epithelial stress in the transition from CD to RCD. A decrease in regulatory T cells (expressing FOXP3), increased cell proliferation (as indicated by Ki67), and heightened MHC II expression may be potential biomarkers for disease severity and progression. These results suggest that therapies targeting these pathways could enhance the management of RCD.