Immunohistochemical evaluation of LGR5, CD71, CD138 and CXCR3 markers in the small bowel mucosa of participants with celiac disease and persons with normal bowel mucosa

Abstract

Celiac disease (CD) is a chronic autoimmune disease of the small bowel mucosa that develops because of the altered immune response to gluten, which leads to intestinal epithelium damage and villous atrophy. However, studies on regeneration of the damaged small bowel mucosa and density of intestinal stem cells (ISC) in CD persons are still scarce. We aimed to evaluate the number of small bowel mucosa cells positive for LGR5, CD138/Syndecan-1, CD71 and CXCR3 in CD and in controls with normal bowel mucosa; to find relationship between these markers and degree of small intestinal atrophy and to compare these results with our previous data about the number of CD103+, IDO + DCs, FOXP3 + Tregs, enterovirus (EV) density and serum zonulin level. Paraffin sections of the small bowel biopsies were obtained from 26 children with CD (median age 6.5 years) and 20 controls with normal intestinal mucosa (median age 14.2 years) and from the tissue bank of the Department of Pathology of Tartu University Hospital (from 18 participants with CD and from 11 with normal small bowel mucosa). The number of LGR5+, CD71 +, CD138+, and CXCR3 + cells was evaluated using immunohistochemistry. The median number of CD138 + and CXCR3 + cells was significantly higher in the small bowel mucosa in CD compared with normal mucosa (p = 0.0002 for CD138 and p = 0.006 for CXCR3). The median number of CD71 + cells was significantly higher in normal small bowel mucosa (p = 0.005). The number of LGR5 + cells did not differ between persons with CD and those with normal small bowel mucosa (p = 0.7). Significant increased number of CD138 + and CXCR3 + cells in the small bowel mucosa of participants with CD confirms their role in pathogenesis of this disease. There was no expected remarkable difference in the density of any of the studied markers between lower or higher grade of small bowel atrophy and level of tTG-IgA in CD.