Intestinal alpha-defensin expression in pediatric inflammatory bowel disease.

BACKGROUND: Reduced alpha-defensin expression has been reported in the terminal ileum (TI) of adult patients with ileal Crohn's disease (CD). However, little is known about alpha-defensin expression in children with chronic inflammatory bowel disease (IBD). METHODS: In all, 283 intestinal biopsies were obtained from children with CD, ulcerative colitis (UC), and healthy controls. Absolute mRNA copy numbers for HD5, HD6, IL-8, Villin 1, and Tcf-4 were analyzed by reverse-transcription polymerase chain reaction (RT-PCR). HD5 immunostaining was performed on biopsy sections and patients genotyped for NOD2 mutations. RESULTS: Equal expression levels of alpha-defensins (HD5 and HD6) were found in TI biopsies of children with ileal CD (L1+L3) compared to patients with colonic disease (L2) and healthy controls. In contrast, we found significantly higher levels of alpha-defensins in the TI of children with UC compared to CD and controls. Reduced expression of Tcf-4 was observed exclusively in the duodenum and TI of CD patients with L1+L3 phenotype. We demonstrate significantly increased expression of HD5 and HD6 in the inflamed colon of IBD children (UC and CD) attributable to the presence of metaplastic Paneth cells. CONCLUSIONS: In this study no difference in alpha-defensin expression was found in the TI of CD children and controls. However, significant reduction of Tcf-4 in L1+L3 phenotype suggests that a possibly impaired PC differentiation may lead to altered HD5 and HD6 expression at some stage of disease. Additionally, substantially increased expression of alpha-defensins in the inflamed colonic mucosa of children with IBD raises the question for their potential involvement in modulating inflammation in these patients.

Limited ileo-caecal resection for localised Crohn's disease in childhood: Clinical outcome and predictors of further surgery.

OBJECTIVES: To investigate the outcome of limited ileo-caecal resection in children with localised Crohn's disease (CD) and determine predictors of further surgery. METHODS: Review of children diagnosed with CD and operated on for ileo-caecal disease from 1995 to 2005. Age at diagnosis, endoscopic disease distribution, indication for surgery, site of recurrence and date of last follow-up were recorded. Surgery required removal of only the ileo-caecal junction and caecal pole with removal of the minimum terminal ileal length. RESULTS: Thirty seven children underwent intestinal resection. Time between primary operation and most recent follow-up was 3.8 years (range 1 month-8.8 years). Indications for surgery were obstruction/stricture (20), treatment-resistant disease (13) and abscess/perforation peritonitis (4). Follow-up was available in 32. Nine (28%) required re-laparotomy. Median time to second laparotomy was 12 months (range 4-58 months). Eighteen children required no endoscopies after surgery (median follow-up 3.4 years). CONCLUSION: Most conservative surgery occurs about 2 years after diagnosis. About 1 in 4 children have a further laparotomy within 12 months. Over half of these require division of adhesions. Limited ileo-caecal resection for localized Crohn's disease is not associated with early peri-anastomotic recurrence. Developments in laparoscopic surgery are likely to further reduce complications from adhesions.

Spontaneous T(H)1 cytokine production by intraepithelial but not circulating T cells in infants with or without food allergies.

BACKGROUND: It has been established that the maintenance of immunological tolerance to dietary antigen and the intestinal flora (oral tolerance) is an actively-maintained process dependent upon mucosal lymphocyte populations. Early life exposures appear critical in the development of such tolerance. However little is known about the activation status of mucosal lymphocytes in human infancy and childhood. PATIENTS AND METHODS: We have performed flow cytometric analysis for cell lineage and cytokine-production status in peripheral blood and duodenal intraepithelial lymphocytes taken during endoscopy from 20 children [median age 2.9 +/- 0.6 years (median +/- SE)] in whom investigation found no intestinal abnormalities (histologically normal controls) and 30 children (median age 1.6 +/- 0.4 years) with confirmed allergy to cow's milk and other dietary antigens. RESULTS: Regardless of clinical status, spontaneous production of cytokines was low or undetectable in peripheral blood cells. By contrast, intraepithelial CD4 and CD8 cells isolated from the small intestine were often activated, with 5% or more showing spontaneous production of T(H)1 type [interleukin-2, interferon (IFN)-gamma] cytokines in both normal controls and food-allergic children. Stimulation in vitro strongly induced cytokine production in peripheral blood but not intraepithelial lymphocytes. Immunohistochemistry showed similar density of IFN-gamma(+) intraepithelial lymphocytes in controls and allergic children. CONCLUSIONS: Duodenal intraepithelial lymphocytes in human infants show a state of increased spontaneous activation compared with peripheral blood lymphocytes, and show no significant impairment of T(H)1 responses in food allergic children.

Response to infliximab is related to disease duration in paediatric Crohn's disease.

BACKGROUND: Infliximab is an effective therapy in adult patients with refractory and fistulizing Crohn's disease. Experience in children is still limited. AIM: : To evaluate the experience in 22 children and adolescents treated with infliximab with refractory and/or fistulizing Crohn's disease, and to compare duration of response in children between early Crohn's disease and late Crohn's disease. METHODS: The experience in 22 children and adolescents treated with a total of 73 infusions was evaluated retrospectively. Treatment indication was refractory Crohn's disease in 9/22 patients, fistulizing Crohn's disease in 7/22 patients and both these conditions in 6/22. All patients with refractory Crohn's disease had late Crohn's disease (> 1 year), whereas 6/13 patients with fistulas had early disease (< 1 year). RESULTS: Mean Paediatric Crohn's Disease Activity Index (PCDAI) decreased from 41.2 to 16.2 at 4 weeks (P < 0.01), and to 15.4 at 18 weeks (P < 0.01). Mean PCDAI at 18 weeks in children with early Crohn's disease and late Crohn's disease was 5.5 and 18.1, respectively (P < 0.05). Complete closure of fistulas was obtained in 5/6 children with early Crohn's disease and in 2/7 children with late Crohn's disease. Immediate adverse reactions were observed in two children. CONCLUSIONS: Infliximab is a highly effective treatment in children and adolescents with both severe refractory or fistulizing Crohn's disease. Children with early Crohn's disease have a higher chance of prolonged response to infliximab than children with late Crohn's disease.