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Background & Aims Potential celiac disease is characterized by positive results from serologic tests for tissue transglutaminase antibodies (anti-TG2) but normal duodenal architecture (Marsh stages 0–1). There is controversy over the best way to manage these patients. We investigated risk factors associated with the development of villous atrophy in children with potential celiac disease. Methods We performed a prospective study of 280 children (ages 2–18 years) in Italy with suspected celiac disease, followed for up to 12 years (range, 18–150 months; median 60 months). The subjects had 2 consecutive positive results from tests for anti-TG2, tested positive for the endomysial antibody (anti-EMA), had total serum levels of immunoglobulin A in the normal range, normal duodenal architecture (Marsh stages 0–1) in 5 biopsies, and HLA DQ2- or DQ8-positive haplotypes. The children underwent serologic tests and clinical analyses every 6 months and a small bowel biopsy was taken every 2 years. A total of 210 patients of the original cohort were assessed at the 9-year follow-up evaluation. We performed multivariate analyses of clinical, genetic, and histologic data to identify factors associated with progression to villous atrophy. Results During the follow-up period, 42 (15%) of 280 children developed villous atrophy, whereas 89 (32%) children no longer tested positive for anti-TG2 or anti-EMA. The cumulative incidence of progression to villous atrophy was 43% at 12 years. In multivariate analysis, the baseline factors most strongly associated with development of villous atrophy were numbers of γδ intraepithelial lymphocyte cells followed by age and homozygosity for the HLA DQB1*02. In discriminant analysis, these baseline factors identified 80% of the children who developed baseline atrophy. Conclusions In a long-term study of 280 children with suspected celiac disease (based on anti-TG2 and anti-EMA) on gluten-containing diets, the cumulative incidence of progression to villous atrophy was 43% over a 12-year period. We identified factors that can be used to identify children at highest risk for villous atrophy. This approach might be used to determine whether children with suspected celiac disease should immediately start a gluten-free diet or be monitored on their regular diet.

BACKGROUND & AIMS: Developing antigen-specific approaches for diagnosis and treatment of celiac disease requires a detailed understanding of the specificity of T cells for gluten. The existing paradigm is that T-cell lines and clones from children differ from those of adults in the hierarchy and diversity of peptide recognition. We aimed to characterize the T-cell response to gluten in children vs adults with celiac disease. METHODS: Forty-one children with biopsy-proven celiac disease (median age, 9 years old; 17 male), who had been on strict gluten-free diets for at least 3 months, were given a 3-day challenge with wheat; blood samples were collected and gluten-specific T cells were measured. We analyzed responses of T cells from these children and from 4 adults with celiac disease to a peptide library and measured T-cell receptor bias. We isolated T-cell clones that recognized dominant peptides and assessed whether gluten peptide recognition was similar between T-cell clones from children and adults. RESULTS: We detected gluten-specific responses by T cells from 30 of the children with celiac disease (73%). T cells from the children recognized the same peptides that were immunogenic to adults with celiac disease; deamidation of peptides increased these responses. Age and time since diagnosis did not affect the magnitude of T-cell responses to dominant peptides. T-cell clones specific for dominant α- or ω-gliadin peptides from children with celiac disease had comparable levels of reactivity to wheat, rye, and barley peptides as T-cell clones from adults with celiac disease. The α-gliadin-specific T cells from children had biases in T-cell receptor usage similar to those in adults. CONCLUSIONS: T cells from children with celiac disease recognize similar gluten peptides as T cells from adults with celiac disease. The findings indicate that peptide-based diagnostics and therapeutics for adults may also be used for children. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Two peptidases have been found in the brush border of rabbit small intestine: dipeptidylaminopeptidase IV, which is able to hydrolyze glycyl-l-proline from glycyl-l-prolyl-β-naphthylamide, and a carboxypeptidase, which is able to hydrolyze N -carbobenzoxy-l-prolyl-l-alanine and is activated by Co 2+ . These enzymes have the highest levels of specific activity in the distal ileum. The enzymatic activities hydrolyzing these substrates were found to be almost totally localized in the brush border: 90 and 99% of carboxypeptidase and dipeptidylaminopeptidase activities, respectively, were recovered in the brush border, assuming 100% recovery of the sucrase activity in this subcellular fraction. Both enzymes were present in the brush border of rabbit fetuses at the end of gestation as well as in the brush border of rabbits 7 days after ligation of the pancreatic duct. These results demonstrate that they are not bacterial or pancreatic enzymes absorbed on the luminal surface of the brush border. The proteins of brush border of rabbit intestine were solubilized by papain digestion and filtered on Sephadex G-200: the electrophoresis on gradient of polyacrylamide gel of the filtered proteins identified six peptidases: the dipeptidylaminopeptidase IV; the carboxypeptidase; the oligoaminopeptidase (substrate l-leucyl-β-naphthylamide); the aminopeptidase A (substrate α-l-glutamyl-β-naphthylamide); and two other peptidases hydrolyzing glycyl-l-leucine and l-methionyl-l-leucine. The demonstration in the brush border of these different peptidases suggests that this subcellular organelle plays a major role in terminal protein digestion, complementary to intraluminal digestion and intracellular digestion.