EARLY EPITHELIAL ALTERATIONS IN "LATENT/AT RISK" CELIAC PATIENTS WITH NORMAL HISTOLOGY

Abstract

Background: Celiac disease (CD) is an intestinal inflammatory disease induced in genetically susceptible people by gluten ingestion. A known mechanism is the adaptive response to immunodominant peptides of α-gliadin recognized by gliadin specific CD4+ T cells in the LP driving the anti-tissue transglutaminase (TTG) antibody response. Mucosal damage is mediated by CD8+ intraepithelial lymphocytes recognizing innate epithelial stress ligands. The α-gliadin p31-49 peptide, unrecognized by CD4+ T cells, triggers epithelial stress. Hypothesis: A subset of "latent/at risk" CD patients with normal histology display markers of stress precluding T cell activation. Methods: 42 underwent duodenal biopsies for GI symptoms, family history(FH) of CD or positive anti-TTG abs. 37 pts with normal histology were divided into controls or "latent/at risk" CD based on HLA-DQ2 or DQ8, presence of anti-TTG abs, or 1st or 2nd-degree FH. Controls did not have a FH or anti-TTG abs. Biopsies were stained for IL-15 and Hsp70 and interpreted by GI path in a blinded manner scoring Hsp70 from 0-3 and IL-15 from 0-4. Results: Increased IL-15 (P < 0.007) and Hsp70 (P < 0.00008) expression was seen in the latent group versus controls. HLA type made no significant difference in expression of either marker. Surprisingly, when analyzed based on TTG ab, epithelial IL-15 (P < 0.006) and Hsp70 (P < 0.001) scores were higher among the TTG neg versus TTG pos and controls, suggesting IL-15 and Hsp70 expression are not linked to the CD4+ response. Conclusions: These results indicate latent CD patients with apparent normal histology and CD4+ response display markers of epithelial cell stress. Aberrant innate responses may play a role without CD4+ activation. Future studies will determine whether high levels of IL-15 and Hsp70 is predictive of overt CD.