Role of CXCR3/CXCL10 axis in immune cell recruitment into the small intestine in celiac disease.

Lymphocytic infiltration in the lamina propria (LP), which is primarily composed of CD4(+) Th1 cells and plasma cells, and increased numbers of intraepithelial lymphocytes (IELs), is a characteristic finding in active celiac disease (CD). Signals for this selective cell recruitment have not been fully established. CXCR3 and its ligands, particularly CXCL10, have been suggested to be one of the most relevant pathways in the attraction of cells into inflamed tissues. In addition, CXCR3 is characteristically expressed by Th1 cells. The aim of this work was to investigate the participation of the chemokine CXCL10/CXCR3 axis in CD pathogenesis. A higher concentration of CXCL10 was found in the serum of untreated CD patients. The mRNA levels of CXCL10 and CXCL11 but not CXCL9 were significantly higher in duodenal biopsies from untreated CD patients compared with non-CD controls or treated patients. The results demonstrate that CXCL10 is abundantly produced in untreated CD and reduced in treated patients, and the expression of CXCL10 was found to be correlated with the IFNγ levels in the tissue. Plasma cells and enterocytes were identified as CXCL10-producing cells. Moreover, the CXCL10 expression in intestinal tissues was upregulated by poly I:C and IL-15. IELs, LP T lymphocytes, and plasma cells, which infiltrate the intestinal mucosa in untreated CD, express CXCR3. The CXCR3/CXCL10 signalling axis is overactivated in the small intestinal mucosa in untreated patients, and this finding explains the specific recruitment of the major cell populations that infiltrate the epithelium and the LP in CD.

Iron, zinc, and copper nutritional status in children infected with Helicobacter pylori.

OBJECTIVE: : Helicobacter pylori colonizes the gastric mucosa of about half of the world's population and it has been related to extragastrointestinal diseases. The present study sought to evaluate the association between H pylori infection and iron, zinc, and copper nutritional status in symptomatic children. PATIENTS AND METHODS: : A cross-sectional study was carried out in 395 children (4-16 years) with upper gastrointestinal symptoms, who were tested for H pylori infection by the C-urea breath test. Iron status was determined by hemoglobin, serum ferritin, and serum transferrin receptors. Copper and zinc serum concentrations were also evaluated. Epidemiological data, dietary assessment, and anthropometric indicators were analyzed as potential confounding factors. RESULTS: : Prevalence of H pylori infection was 24.3%. Anemia and iron deficiency (ID) were found in 12.0% and 14.3% of the H pylori-positive and 8.9% and 11.0% of the H pylori-negative children, respectively. There was no association between H pylori infection and anemia (odds ratio = 1.54 [95% confidence interval [CI] 0.73%-3.24%]) or ID (odds ratio = 1.35 [95% CI 0.67-2.70]). Crude beta coefficients showed that H pylori has no significant effect on hemoglobin, serum ferritin, serum transferrin receptors, copper, and zinc concentrations. However, adjusted results suggested that H pylori-infected children had an increase of 9.74 microg/dL (95% CI 2.12-17.37 microg/dL) in copper concentrations. CONCLUSIONS: : This study revealed that H pylori infection was not associated with iron deficiency, anemia, or zinc concentrations; however, a positive relation with copper status was found after adjusting for confounding factors. The contribution of H pylori infection to higher copper concentrations needs to be confirmed by additional studies.

Histopathologic diagnosis of celiac disease in children without clinical evidence of malabsorption.

Diverse clinical and pathologic experiences seem to have led to the idea that celiac disease is a spectrum in both categories. Conflicting results emerging from different reports have produced a large amount of confusion on the subject. This article discussed histopathology findings in 10 children with positive autoantibodies for celiac disease but without clinical evidence of malabsorption. The patients were evaluated following a detailed video-endoscopic study sampling the proximal (first and second) and distal (third and fourth) duodenal parts separately and processed apart. The procedure consistently revealed advanced villous atrophy in the proximal duodenal mucosa associated with mild to absent involvement of the distal segments. The data here presented favor the interpretation that (1) the presence of autoantibodies for celiac disease is always associated with mucosal damage, (2) mucosal damage in the absence of malabsorption is always evident in the proximal duodenum, and (3) the mucosal biopsy in search for the telltale damage needs to be done in separate samples of proximal and distal duodenal mucosa. This procedure may result in a better understanding of the dynamics of mucosal damage in celiac disease.

Effect of a probiotic food as an adjuvant to triple therapy for eradication of Helicobacter pylori infection in children.

OBJECTIVE: Current recommendations for treatment of Helicobacter pylori infection include a proton pump inhibitor in combination with two antibiotics. We evaluated the potential activity of a probiotic food as an adjuvant to antibiotic triple therapy for eradication of H. pylori infection in children from Buenos Aires, Argentina. METHODS: Sixty-five children who tested positive for H. pylori, as diagnosed by (13)C-urea breath test and endoscopy, were included in this study. Patients were randomized to receive 1-wk triple therapy plus probiotic food (treated group) or milk placebo (control) that was administered for 3 mo. Probiotic food consisted of 250 mL of a commercial yogurt containing Bifidobacterium animalis and Lactobacillus casei (10(7) colony-forming units/mL). Post-treatment urea breath test controls were performed 1 and 3 mo after the end of triple therapy. RESULTS: We found no significant differences in H. pylori eradication rates (ERs) at 1 and 3 mo between the treated group (ER = 45.5% and 42.4%) and the control group (ER = 37.5% and 40.6%). Relative risks between groups were 0.87 (95% confidence interval 0.58-1.32, P = 0.345) in the first month and 0.97 (95% confidence interval 0.64-1.46, P = 0.542) in the third month. CONCLUSIONS: We could not demonstrate an adjuvant effect of the studied probiotic food to triple therapy in the eradication of H. pylori infection in children in Buenos Aires, Argentina. However, we found lower ERs than those reported for the same therapeutic scheme in developed countries, indicating that bacterial resistance and alternative therapeutic strategies should be studied.

Histologic findings in "ex- Helicobacter pylori" gastric biopsies of pediatric patients.

Long-term sequelae of Helicobacter pylori-associated chronic gastritis (HpCG) have been described in adult patients. In the present study we report the histology of gastric mucosa biopsies in 6 asymptomatic pediatric patients (5 male and 1 female; mean age 9.5 years) with previous HpCG. Preceding H. pylori was histologically proved and confirmed by culture, direct visualization, and/or serology before delivering treatment. In 5 of 6 cases the HpCG followed a protracted clinical course, with various therapeutic series needed before H. pylori eradication. Time from final treatment for HpCG to actual biopsy ranged from 3 months to almost 3 years. Gastric mucosa showed mild chronic gastritis with absence of H. pylori organisms (6 of 6), focal loss of gland units with collagenous replacement (6 of 6), serrated foveolae (3 of 6), regenerative changes at elongated glandular necks with cells having enlarged and hyperchromatic nuclei (5 of 6), lymphoid aggregates (2 of 6), and presence of sulfomucins in isolated epithelial cells of glands and foveolae (2 of 6). None of these features were noticed in 10 normal gastric mucosa biopsies used as controls. The referred findings in "ex- H. pylori" pediatric patients may represent very early sequelae from HpCG at this age.