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Objectives: The aim of this study was to identify new markers of mucosal T cells to monitor ongoing intestinal immune responses in peripheral blood., Methods: Expression of cell-surface markers was studied in mice on ovalbumin (OVA)-specific T cells in the gut-draining mesenteric lymph nodes (MLN) after OVA feed. The effect of the local mucosal mediators retinoic acid (RA) and transforming growth factor-β (TGF-β) on the induction of a mucosal phenotype was determined in in vitro T-cell differentiation assays with murine and human T cells. Tetramer stainings were performed to study gluten-specific T cells in the circulation of patients with celiac disease, a chronic small-intestinal inflammation., Results: In mice, proliferating T cells in MLN were CD62L(neg)CD38(+) during both tolerance induction and abrogation of intestinal homeostasis. This mucosal CD62L(neg)CD38(+) T-cell phenotype was efficiently induced by RA and TGF-β in mice, whereas for human CD4(+) T cells RA alone was sufficient. The CD4(+)CD62L(neg)CD38(+) T-cell phenotype could be used to identify T cells with mucosal origin in human peripheral blood, as expression of the gut-homing chemokine receptor CCR9 and β(7) integrin were highly enriched in this subset whereas expression of cutaneous leukocyte-associated antigen was almost absent. Tetramer staining revealed that gluten-specific T cells appearing in blood of treated celiac disease patients after oral gluten challenge were predominantly CD4(+)CD62L(neg)CD38(+). The total percentage of circulating CD62L(neg)CD38(+) of CD4 T cells was not an indicator of intestinal inflammation as percentages did not differ between pediatric celiac disease patients, inflammatory bowel disease patients and respective controls. However, the phenotypic selection of mucosal T cells allowed cytokine profiling as upon restimulation of CD62L(neg)CD38(+) cells interleukin-10 (IL-10) and interferon-γ (IFN-γ) transcripts were readily detected in circulating mucosal T cells., Conclusions: By selecting for CD62L(neg)CD38(+) expression that comprises 5-10% of the cells within the total CD4(+) T-cell pool we are able to highly enrich for effector T cells with specificity for mucosal antigens. This is of pivotal importance for functional studies as this purification enhances the sensitivity of cytokine detection and cellular activation.

Objectives: Acute severe ulcerative colitis (ASC) is a potentially life-threatening disease. We aimed to formulate guidelines for managing ASC in children based on systematic review of the literature and robust consensus process. This manuscript is a product of a joint effort of the ECCO (European Crohn's and Colitis Organization), the Pediatric Porto Inflammatory Bowel Disease (IBD) Working group of ESPGHAN (European Society of Pediatric Gastroenterology, Hepatology, and Nutrition) and ESPGHAN., Methods: A group of 19 experts in pediatric IBD participated in an iterative consensus process including two face-to-face meetings. A total of 17 predefined questions were addressed by working subgroups based on a systematic review of the literature., Results: The recommendations and practice points were eventually endorsed with a consensus rate of at least 95% regarding: definitions, initial evaluation, standard therapy, timing of second-line therapy, the role of endoscopic evaluation and heparin prophylaxis, how to administer second-line medical therapy, how to assess response, surgical considerations, and discharge recommendations. A management flowchart is presented based on daily scoring of the Pediatric Ulcerative Colitis Activity Index (PUCAI), along with 28 formal recommendations and 34 practice points., Conclusions: These guidelines provide clinically useful points to guide the management of ASC in children. Taken together, the recommendations offer a standardized protocol that allows effective monitoring of disease progress and timely treatment escalation when needed.

Objectives: Food allergy and celiac disease may lead to childhood constipation. Early introduction of food allergens and gluten in the first year of life has been suggested to have a function in these food intolerances, but it is unclear whether this also holds true for development of childhood constipation. The aim of this study was to assess the association between the timing of introduction of food allergens and gluten early in life and functional constipation in childhood., Methods: This study was embedded in the Generation R study, a population-based prospective cohort study from fetal life until young adulthood. Functional constipation at 24 months of age was defined in 4,651 children according to the Rome II criteria of defecation frequency <3 times a week or the presence of mainly hard feces for at least 2 weeks., Results: At the age of 24 months, 12% of the children had functional constipation. Children with functional constipation got introduced to gluten more often before or at the age of 6 months than children without functional constipation (37% and 27%, respectively). After adjustment for birth weight, gestational age, gender, ethnicity, maternal education, and family history of atopy and chronic intestinal disorders, functional constipation was significantly associated with early gluten introduction (odds ratio (OR): 1.35; 95% confidence interval (CI): 1.10-1.65). No association was found between timing of introduction of cow's milk, hen's egg, soy, peanuts, and tree nuts with functional constipation. A history of cow's milk allergy in the first year of life was significantly associated with functional constipation in childhood (OR: 1.57; 95% CI: 1.04-2.36)., Conclusions: These results suggest that early gluten introduction in the first year of life provide a trigger for functional constipation in a subset of children. In case of functional constipation, there also might be a role for cow's milk allergy initiated in the first year of life.

Objective: The aim of this study was to assess the efficacy and safety of a single infusion of infliximab in the treatment of pediatric Crohn's disease (CD)., Methods: A total of 21 pediatric CD patients were enrolled at seven study centers and randomized to receive a single infusion of infliximab 1 mg/kg (n = 6), 5 mg/kg (n = 7), or 10 mg/kg (n = 8) over at least 2 hrs at week 0 in this multicenter, open-label, dose-blinded trial. Efficacy assessments, including the Pediatric Crohn's Disease Activity Index (PCDAI), modified CDAI, C-reactive protein concentration (CRP), and erythrocyte sedimentation rate (ESR) determinations, were made at screening and at weeks 1, 2, 4, 8, and 12. Adverse events were assessed throughout study participation., Results: Improvements in the PCDAI, modified CDAI, ESR, and CRP were observed with all infliximab doses, beginning at week 1. On average, all treated patients experienced approximately 50% improvement in the PCDAI by week 2. By week 12, the PCDAI remained approximately 30% improved from baseline. During the study, all 21 patients (100%) achieved a clinical response, and 10 patients (48%) achieved clinical remission. There were no infusion reactions in any of the treatment arms., Conclusions: The results of this trial suggest that infliximab may be safe and effective as short-term therapy of medically refractory moderate to severe CD in a pediatric population.