Urszula Grzybowska-Chlebowczyk

Fecal pyruvate kinase: a potential new marker for intestinal inflammation in children with inflammatory bowel disease.

Objective. Inflammatory bowel disease (IBD) in children creates diagnostic and clinical challenges. Clinical data, endoscopic appearance and the histopathological assessment of biopsies are essential for diagnosis. However, new methods are required for non-invasive follow-up. Recently, we demonstrated that the dimeric isoform of pyruvate kinase (PK) detected in stool might serve as a potential non-invasive screening tool in inflamed pouch mucosa. The aim of this study was to investigate whether this test could be used to detect intestinal inflammation in pediatric IBD patients. Material and methods. Fecal PK immunoreactivity was assessed in 75 patients with proven ulcerative colitis (UC) and 32 with Crohns disease (CD). Pediatric Crohn Disease Activity Index (PCDAI) and Truelove-Witts scores were determined in CD and UC patients, respectively. Thirty-five healthy subjects (HS) served as a control group. Results. Increased PK levels were documented in 94.1% and 100% active CD patients with a cut-off level of 5 U/g and a cut-off level of 4 U/g, respectively, and in 94.3% of active UC patients regardless of cut-off level. Enzyme immunoreactivity was significantly higher in all IBD patients than in HS. Abnormal PK results were documented in 71.7% of all IBD patients (65.3% and 84.4 for UC and CD patients, respectively). Enzyme levels in UC remission were significantly lower than in the active phase. Enzyme immunoreactivity significantly correlated to both scoring systems. Conclusions. The measurement of stool PK could be a potentially useful marker of IBD activity in children. However, its clinical value demands further studies for comparison with other tests.

Immunogenecity of hepatitis A vaccine in pediatric patients with inflammatory bowel disease.

Background: There are only a few studies on immune response to routine vaccinations in children with inflammatory bowel disease (IBD), despite a strong need for this kind of study. The aim of the study was to evaluate the immunogenicity of an inactivated hepatitis A vaccine (HAV) in IBD pediatric patients compared with healthy controls. Methods: This was an open, prospective, and controlled study on anti‐HAV‐negative children and adolescents age 2‐18 years with IBD. HAV using 720 enzyme‐linked immunosorbent assay (ELISA) units were administered at 0 months and at 6‐12 months. Seroconversion and geometric mean titers were measured after each vaccine dose. The evidence of local and systemic adverse effects for 3 days after the first and second dose of vaccine was registered. Results: A total of 134 subjects (66 patients and 68 controls) completed the whole study course consisting of two doses of vaccine and six serum samples. There was no significant difference in the rate of seroconversion between IBD patients and controls when measured after the second dose of vaccine (97% versus 100%, P = 0.2407), but the rate was significantly lower in the IBD group when measured after the first dose (39% versus 64%, P = 0.00001). The mean geometric titers were statistically significantly lower in the IBD group than in the control group at all of the measured timepoints. There were no serious adverse events related to HAV during the study. Conclusions: HAV is both immunogenic and safe in pediatric patients with IBD. (Inflamm Bowel Dis 2010;)

Prevalence and correlates of vitamin K deficiency in children with inflammatory bowel disease

Although vitamin K deficiency has been implicated in adult inflammatory bowel disease (IBD), its prevalence in pediatric IBD remains unknown. We carried out a cross-sectional study in 63 children with Crohns disease (CD) and 48 with ulcerative colitis (UC) to assess the prevalence of vitamin K deficiency and to search for potential correlation between vitamin K status and pediatric IBD activity. Vitamin K status was assessed using protein induced by vitamin K absence-II (PIVKA-II; ELISA). Prevalence of vitamin K deficiency was 54.0% in CD and 43.7% in UC. Vitamin K deficiency was more common in patients with higher CD activity, in CD patients with higher mass Z-scores, and less common among children with CD treated with infliximab. Relation of vitamin K deficiency to pediatric IBD clinical course and treatment demand further research.

Monotherapy with infliximab versus combination therapy in the maintenance of clinical remission in children with moderate to severe Crohn disease.

Objectives: The aim of the present study was to compare the efficacy and safety of 2 protocols of maintenance therapy with infliximab (IFX) and an immunomodulatory agent in pediatric patients with Crohn disease (CD): withdrawal of immunomodulators versus continuation of immunosuppressants. Methods: The present multicenter randomized open-label trial included 99 patients with CD (ages 14.5 ± 2.6 years) who were administered IFX (5 mg/kg body weight) along with an immunomodulatory agent (azathioprine 1.5–3 mg/kg body weight per day, methotrexate 10–25 mg/week). After 10 weeks of the induction therapy, 84 responders were centrally randomized into 1 of the following groups: group I (n = 45) in which IFX and an immunomodulatory agent were continued up to week 54 and group II (n = 39) in which the immunomodulatory agent was discontinued after 26 weeks. Results: The induction therapy was reflected by a significant decrease in Pediatric Crohns Disease Activity Index (PCDAI) and Simplified Endoscopic Activity Score for Crohns Disease (SES-CD) values. After the maintenance phase, the analyzed groups did not differ significantly in terms of the clinical response loss rates and final PCDAI and SES-CD scores. Furthermore, no significant intragroup differences were documented between mean PCDAI scores determined at the end of induction and maintenance phases. Intensification/modification of the treatment was required in 13 of 45 (29%) and 11 of 39 (28%) patients of groups I and II, respectively. A total of 9 serious adverse events were documented; none of the patients died during the trial. Conclusions: Twenty-six weeks likely represent the safe duration of combined IFX/immunomodulatory therapy in our sample of pediatric patients with CD.

Lack of effect of Lactobacillus GG in breast-fed infants with rectal bleeding : A pilot double-blind randomized controlled trial

Objectives: For breast-fed infants with rectal bleeding, maternal restriction of dietary protein such as cows milk proteins is often recommended; however, poor response to dietary protein restriction is of concern. This pilot study was designed to assess the effectiveness of Lactobacillus GG (LGG) in breast-fed infants with rectal bleeding. Patients and Methods: Breast-fed infants <6 months of age with rectal bleeding (defined as the presence of visible specks or streaks of blood mixed with mucus in the stool in otherwise healthy infants) were enrolled in a double-blind randomized controlled trial in which they received LGG 3 × 109 colony-forming units (n = 14) or placebo (n = 15) twice daily for 4 weeks as an adjunct to cows milk restriction in the mothers diet. Analyses were based on allocated treatment and included data from 26 infants. Results: Mean duration of rectal bleeding was similar in the LGG and control groups (17.3 ± 10.6 vs 15.4 ± 11 days; mean difference −1.9 (95% confidence interval [CI] −4 to 7). No difference was found in the number of infants with clinical resolution of rectal bleeding within 72 hours and no relapse afterward (2/11 vs 3/15, relative risk [RR] 0.9, 95% CI 0.2–3.9) and the number of infants with clinical resolution of rectal bleeding within 72 hours followed by relapse of symptoms (5/11 vs 5/15, RR 1.4, 95% CI 0.5–3.5). Breast-feeding cessation was not needed in any infant. Conclusions: These results do not support the use of LGG as an adjunct to maternal cows milk restriction in breast-fed infants with rectal bleeding.

Usefulness of Faecal Calprotectin Measurement in Children with Various Types of Inflammatory Bowel Disease

Introduction. The aim of the study was to assess the usefulness of the FC measurement in children with various types of IBD and relation to the disease activity. Patients and Methods. 91 patients (49 boys: 53.85% and 42 girls: 46.15%, mean age: 13.38 years, range 6–18 years) were included in the analysis. Patients were divided into the groups: B1—24 children with CD, B2—16 patients with UC, and a group comprising 31 children with other types of colitis; the control group (K) comprised 20 healthy children. FC was assayed by ELISA method, using Phical test (Calpro). Results. The mean faecal calprotectin concentrations were higher in children with CD and UC as compared to healthy controls, patients with eosinophilic, lymphocytic, and nonspecific colitis. A positive correlation was observed between FC concentrations and the disease activity (the PCDAI scale, the Truelove-Witts Scale, and the endoscopic Rachmilewitz Index). Conclusion. It seems that the FC concentrations can be a useful, safe, and noninvasive test in children suspected for IBD, since FC concentration is higher in children with CD and UC than in patients with other inflammatory diseases.

Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota - Key players in the pathogenesis of celiac disease

Celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens (HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive (specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiota homeostasis, epithelial layer integrity, and the gut-associated lymphoid tissue with its intraepithelial lymphocytes (IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.

Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population.

Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn’s disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10−11 and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components.

Disaccharidase activity in children with inflammatory bowel disease.

BACKGROUND/AIMS The etiopathogenesis of inflammatory bowel disease (IBD) is multifactorial and not well explained. Environmental, genetic, and dietary factors play an important role. The aim of the study was the evaluation of lactase, saccharase, and maltase activity in patients with IBD. MATERIALS AND METHODS The study comprised 65 children, aged 3-18 years. During a routine endoscopy, we took biopsies from the descending part of the duodenum. In these biopsies, we determined disaccharidase activity using Dahlquists method. RESULTS Decreased lactase activity in the biopsies taken from the small intestine mucosa was most frequently observed in patients with Crohns disease (5/15-33%) and least frequently seen in children with lymphocytic colitis (in 1/10-10%). The lowest mean values of lactase activity were found in the children with Crohns disease and ulcerative colitis (1.7-2.5 U/1 g). Decreased saccharase activity in the biopsies obtained from the small intestine mucosa was most frequently observed in patients with lymphocytic colitis (in 5/10-50%) and ulcerative colitis (9/20-45%) and least frequently seen in children with non-specific undetermined colitis (in 7/20-35%). Decreased maltase activity in the small bowel mucosa was the most frequently observed in patients with Crohns disease (in 5/15-33%) and least frequently seen in children with ulcerative colitis (in 3/20-15%). The lowest mean values of maltase activity were found in the children with Crohns disease (5.4 U/1 g). CONCLUSION Therefore, it seems reasonable to perform diagnostic examinations aimed at lactose, saccharose, and maltose intolerance and to initiate a dietary regimen in children with IBD.

Influenza vaccination coverage in children with inflammatory bowel disease.

The aim of this study was to evaluate the influenza vaccination status among paediatric patients with inflammatory bowel disease (IBD) in Poland. This was a questionnaire‐based study. 242 patients with IBD and 142 controls were enrolled in the study. Of patients with IBD, 7·8% received an influenza vaccine, compared to 18·3% of controls (P = 0·0013). There were no statistically significant differences in time from IBD diagnosis, disease activity and in drugs, between vaccinated and non‐vaccinated IBD children. In conclusion, the data of our study demonstrate an alarmingly poor influenza vaccination status in the majority of children with IBD. Therefore, there is an unmet need to implement better influenza vaccination strategies for this group of patients.