Sibylle Koletzko

Ludwig-Maximilian-University of Munich, München, Bavaria, Germany

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Publications (303)1302.06 Total impact

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    ABSTRACT: Background Vitamin D is well recognized for its role in skeletal health and its involvement in the modulation of the immune system. In the literature, controversial results are reported for atopic diseases. Thus, we investigated the association between vitamin D status and the prevalence of atopic diseases.Methods Serum 25-hydroxy-vitamin D (25(OH)D) concentrations were measured in a sample of 2815 10-years old children from two German birth cohort studies. Self-reported physician-diagnosed eczema, hay fever or allergic rhinitis, and asthma were used as outcome variables as well as specific IgE positivity against common allergens. We applied logistic regression models, deriving adjusted odds ratio estimates (aOR) and 95% confidence intervals (CI).ResultsFor asthma and hay fever or allergic rhinitis, no associations existed with serum 25(OH)D concentrations. We observed a significant positive relationship between serum 25(OH)D levels and eczema at age 10 (aOR¿=¿1.09, CI¿=¿1.01-1.17, per 10 nmol/l increase in serum 25(OH)D levels) and for the lifetime prevalence of eczema (aOR¿=¿1.05, CI¿=¿1.01-1.09). Specific IgE positivity for food allergens (aOR¿=¿1.07, CI¿=¿1.02-1.11) and aeroallergens (aOR¿=¿1.05, CI¿=¿1.01-1.08) at age 10, as well as lifetime prevalence, was significantly related to the vitamin D status.Conclusion In this study we found no indication that higher blood 25(OH)D levels are associated with decreased risk for any of the atopic outcomes in children. However, we observed a positive association of serum 25(OH)D concentrations with eczema and detectable specific IgE. Due to the given limitations of our study, the clinical relevance of these findings needs further clarification.
    BMC Pediatrics 11/2014; 14(1):286. · 1.92 Impact Factor
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    ABSTRACT: Aim Residential mobility during childhood has been associated with several adverse health outcomes. The present study investigates the influence of residential mobility during childhood measured by the frequency of moves, the child’s age at the time of the move and the total distance moved on the development of behavioural problems in school-age children. Subject and methods Data (N = 2,933) of two German population-based, prospective birth-cohort studies were used. Measurement of children’s residential mobility is based on the addresses at birth, 2, 6 and 10 years, which were collected by questionnaires and subsequently geocoded. Behavioural outcomes were assessed using the Strengths and Difficulties Questionnaire applied at 10-year follow-up. Multiple logistic regression analyses controlling for sex and age of the child, study centre, parental educational level, mother’s age at birth, single parent status and child’s time spent in front of a screen were applied. Results Children with two or more relocations—odds ratio (OR) = 1.95, 95 % confidence interval (CI) = 1.23–3.11—who moved at school age (OR = 1.97, CI = 1.17–3.31) or who moved more than 50 km in total (OR = 1.76, CI = 1.03–3.00) showed a significantly increased risk for the development of behavioural problems measured by the Total Difficulties Score compared to children who have never moved. Moving during early childhood and moving only short distance (less than 10 km in total) were not associated with behavioural problems. Conclusion Increased residential mobility during childhood and especially moves at school age may negatively affect children’s later behaviour. Prevention may consist in parental or teacher’s support of children to cope with moving.
    Journal of Public Health 10/2014; 21(1). · 2.06 Impact Factor
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    ABSTRACT: Background A window of opportunity has been suggested for reducing the risk of celiac disease by introducing gluten to infants at 4 to 6 months of age. Methods We performed a multicenter, randomized, double-blind, placebo-controlled dietary-intervention study involving 944 children who were positive for HLA-DQ2 or HLA-DQ8 and had at least one first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies were periodically measured. The primary outcome was the frequency of biopsy-confirmed celiac disease at 3 years of age. Results Celiac disease was confirmed by means of biopsies in 77 children. To avoid underestimation of the frequency of celiac disease, 3 additional children who received a diagnosis of celiac disease according to the 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria (without having undergone biopsies) were included in the analyses (80 children; median age, 2.8 years; 59% were girls). The cumulative incidence of celiac disease among patients 3 years of age was 5.2% (95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95% CI, 3.7 to 8.1] and 4.5% [95% CI, 2.5 to 6.5], respectively; hazard ratio in the gluten group, 1.23; 95% CI, 0.79 to 1.91). Rates of elevated levels of anti-transglutaminase type 2 and antigliadin antibodies were also similar in the two study groups (7.0% [95% CI, 4.7 to 9.4] in the gluten group and 5.7% [95% CI, 3.5 to 7.9] in the placebo group; hazard ratio, 1.14; 95% CI, 0.76 to 1.73). Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention. Conclusions As compared with placebo, the introduction of small quantities of gluten at 16 to 24 weeks of age did not reduce the risk of celiac disease by 3 years of age in this group of high-risk children. (Funded by the European Commission and others; PreventCD Current Controlled Trials number, ISRCTN74582487 .).
    New England Journal of Medicine 10/2014; 371(14):1304-1315. · 54.42 Impact Factor
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    ABSTRACT: Background and aims Measurement of 7 alpha-hydroxy-4-cholesten-3-one (C4) in serum is a semiquantitative test for bile acid malabsorption (BAM). We have previously established pediatric normal values for C4 with an upper limit of normal of 66.5 ng/mL, independent of age and sex. Here we performed the C4 test in 58 pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC). Methods C4 was measured using high performance liquid chromatography (HPLC) in fasting serum samples of 44 patients with CD (range 7–19 years) and 14 with UC (4–18 years). Disease activity was assessed by the pediatric CD and UC activity indices (PCDAI and PUCAI, respectively) plus serum (CRP, ESR) and fecal inflammatory markers (calprotectin). Results C4 concentrations were increased in 10 CD (23%) (range: 70.8–269.3 ng/mL) but only one UC patient (72.9 ng/mL). CD patients with diarrhea (n = 12) had higher C4-values compared to those without (76.9 vs. 30.4 ng/mL; p = 0.0043). Ileal resection in CD patients (n = 10) was associated with increased C4 concentrations (81.2 vs. 24.3 ng/mL, p = 0.0004). No correlation was found between C4 values and inflammatory markers. Six of 7 CD patients with persistent diarrhea but quiescent disease (PCDAI ≤ 12.5) had C4 values indicating BAM. Conclusion Elevated C4 concentrations indicating BAM are common in children with CD. They are associated with ileal resection and non-bloody diarrhea in the absence of active disease or elevated inflammatory markers. The C4-test identifies a subgroup of CD patients with persistent diarrhea in spite of clinical remission which may benefit from bile acid binding therapy.
    Journal of Crohn s and Colitis 09/2014; · 3.56 Impact Factor
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    ABSTRACT: Patients with a diverse spectrum of rare genetic disorders can present with inflammatory bowel diseases (monogenic IBD). Patients with these disorders often develop symptoms during infancy or early childhood, along with endoscopic or histologic features of Crohn's disease, ulcerative colitis or IBD unclassified. Defects in interleukin 10 signaling have a Mendelian inheritance pattern with complete penetrance of intestinal inflammation. Several genetic defects that disturb intestinal epithelial barrier function or affect innate and adaptive immune function have incomplete penetrance of the IBD-like phenotype. Several of these monogenic conditions do not respond to conventional therapy and are associated with high morbidity and mortality. Due to the broad spectrum of these extremely rare diseases, a correct diagnosis is frequently a challenge and often delayed. In many cases, these diseases cannot be categorized based on standard histologic and immunologic features of IBD. Genetic analysis is required to identify the cause of the disorder and offer the patient appropriate treatment options, which include medical therapy, surgery, or allogeneic hematopoietic stem cell transplantation. In addition, diagnosis based on genetic analysis can lead to genetic counseling for family members of patients. We describe key intestinal, extra-intestinal, and laboratory features of 50 genetic variants associated with IBD-like intestinal inflammation. We provide approaches for identifying patients likely to have these disorders. We discuss classical approaches to identify these variants in patients, starting with phenotypic and functional assessments that lead to analysis of candidate genes. As a complementary approach, we discuss parallel genetic screening using next-generation sequencing followed by functional confirmation of genetic defects.
    Gastroenterology 07/2014; · 12.82 Impact Factor
  • Zeitschrift fur Gastroenterologie. 07/2014; 52(7):711-743.
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    ABSTRACT: AIM: We investigated whether objectively measured access to urban green spaces is associated with behavioural problems in 10-year old children living in Munich and its surrounding areas. METHODS: Behavioural problems were assessed in the GINIplus and LISAplus 10-year follow-up between 2006 and 2009 using the Strengths and Difficulties Questionnaire. Access to green spaces was defined using the distance from a child's residence to the nearest urban green space. Associations between access to urban green spaces and behavioural problems were assessed using proportional odds and logistic regression models in 1932 children with complete exposure, outcome and covariate data. RESULTS: The distance between a child's residence and the nearest urban green space was positively associated with the odds of hyperactivity/inattention, especially among children with abnormal values compared to children with borderline or normal values (odds ratio (OR)=1.20 (95% confidence interval (CI)=1.01-1.42) per 500m increase in distance). When stratified by sex, this association was only statistically significant among males. Children living further than 500m away from urban green spaces had more overall behavioural problems than those living within 500m of urban green spaces (proportional OR=1.41 (95% CI=1.06-1.87)). Behavioural problems were not associated with the distance to forests or with residential surrounding greenness. CONCLUSION: Poor access to urban green spaces was associated with behavioural problems in 10-year old children. Results were most consistent with hyperactivity/inattention problems.
    Environment International 06/2014; 71C:29-35. · 5.66 Impact Factor
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    ABSTRACT: Crohn disease is an inflammatory bowel disease (IBD) with a complex mode of inheritance. Although nucleotide binding and oligomerization domain containing 2 (NOD2) is the strongest risk factor, the cause of Crohn disease remains unknown in the majority of the cases. X-linked inhibitor of apoptosis (XIAP) deficiency causes X-linked lymphoproliferative syndrome type 2. IBD has been reported in some XIAP-deficient patients.
    Journal of Allergy and Clinical Immunology 06/2014; · 11.25 Impact Factor
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    ABSTRACT: Although rotavirus (RV) vaccination was licensed in 2006, it was not included into the officially recommended German childhood vaccination schedule until 2013. Local differences in health policies in the past led to large differences in vaccination coverage rate between the federal states of Germany. This enables an ecologic study of RV vaccine effectiveness.
    The Pediatric Infectious Disease Journal 06/2014; · 3.14 Impact Factor
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    ABSTRACT: Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.
    Journal of Crohn's & colitis. 06/2014;
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    ABSTRACT: Positive greenness effects on health are increasingly reported, although studies on allergic outcomes remain limited and conflicting. We examined whether residential greenness is associated with childhood doctor diagnosed allergic rhinitis, eyes and nose symptoms and aeroallergen sensitisation using two combined birth cohorts (GINIplus and LISAplus) followed from birth to 10 years in northern and southern Germany (Ntotal=5803).
    Journal of Epidemiology &amp Community Health 05/2014; · 3.29 Impact Factor
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    ABSTRACT: Background/Objectives:Mother's body mass index (BMI) is a strong predictor of child BMI. Whether mother's BMI correlates with child's food intake is unclear. We investigated associations between mother's BMI/overweight and child's food intake using data from two German birth cohorts.Subjects/Methods:Food intakes from 3230 participants were derived from parent-completed food frequency questionnaires. Intakes of 11 food groups were categorized into three levels using group- and sex-specific tertile cutoffs. Mother's BMI and overweight were calculated on the basis of questionnaire data. Multinomial regression models assessed associations between a child's food intake and mother's BMI/overweight. Linear regression models assessed associations between a child's total energy intake and mother's BMI. Models were adjusted for study region, maternal education, child's age, sex, pubertal status and energy intake and the BMIs of the child and father.Results:Mothers' BMI was associated with high meat intake in children (adjusted relative risk ratio (RRR (95% confidence interval))=1.06 (1.03; 1.09)). Mothers' overweight was associated with the meat intake (medium versus low RRR=1.30 (1.07; 1.59); high versus low RRR=1.50 (1.19; 1.89)) and egg intake (medium versus low RRR=1.24 (1.02; 1.50); high versus low RRR=1.30 (1.07; 1.60)) of children. There were no consistent associations for rest of the food groups. For every one-unit increase in mothers' BMI, the total energy intake in children increased by 9.2 kcal (3.7; 14.7). However, this effect was not significant after adjusting for children's BMI.Conclusions:Our results suggest that mother's BMI and mother's overweight are important correlates of a child's intake of energy, meat and eggs.European Journal of Clinical Nutrition advance online publication, 21 May 2014; doi:10.1038/ejcn.2014.92.
    European Journal of Clinical Nutrition 05/2014; · 2.95 Impact Factor
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    ABSTRACT: According to Ulrich's psychoevolutionary theory, contact with green environments mitigates stress by activating the parasympathetic system, (specifically, by decreasing blood pressure (BP)). Experimental studies have confirmed this biological effect. However, greenness effects on BP have not yet been explored using an observational study design. We assessed whether surrounding residential greenness is associated with BP in 10 year-old German children.
    BMC Public Health 05/2014; 14(1):477. · 2.32 Impact Factor
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    Joachim Heinrich, Berthold Koletzko, Sibylle Koletzko
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    ABSTRACT: The timing of the introduction of complementary foods appears crucial to the development of allergic diseases later in life. The results from recent observational studies might be misinterpreted to suggest that introducing complementary food prior to the age of four months might have a beneficial effect on the induction of immune tolerance. Since these two recently published papers cannot completely account for reverse causation, as is the case for all observational studies, we recommend that the current ESPGHAN and American Academy of Pediatrics recommendations be maintained as long as new evidence from large randomized controlled intervention trials do not suggest otherwise. That is, complementary foods should be first introduced between the age of 17 to 26 weeks.
    Expert Review of Clinical Immunology 05/2014; · 3.34 Impact Factor
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    ABSTRACT: Faecal calprotectin is used as a sensitive marker for gastrointestinal mucosal inflammation. We compared the performance of three different assays in a large cohort of symptomatic paediatric patients. Retrospective monocentric study. Inpatients and outpatients of a tertiary referral centre for paediatric gastroenterology. 304 symptomatic patients (163 males, aged 2-20 years) with active inflammatory bowel disease (IBD/A, n=130), IBD in clinical remission (IBD/R, n=62), other intestinal diseases (n=45) and controls without identified intestinal disease (n=67). Calprotectin was measured in homogenised faecal samples with three tests (A: EliA Calprotectin, Phadia AB, Sweden; B: PhiCal, Calpro AS, Norway; C: EK-Cal, Bühlmann Laboratories, Switzerland). Concordance between tests was calculated using Kendall's τ coefficient. IBD/A and controls were correctly classified as 97.7%/82.1% (A), 97.7%/85.1% (B) and 98.4%/62.7% (C; not significant). Test C tended to have higher calprotectin values with a lower specificity compared to tests A and B. The concordance between two tests was 0.835 for tests A and B, 0.782 for tests A and C and 0.765 for tests B and C. All three tests are very sensitive for detecting mucosal inflammation, but major differences exist between specificity and absolute values. It is highly advisable to use the test of the same manufacturer for follow-up and to monitor for disease activity.
    BMJ Open 05/2014; 4(5):e004558. · 2.06 Impact Factor
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    ABSTRACT: Objective To investigate whether birth by cesarean delivery rather than vaginal delivery is a risk factor for later childhood obesity. Study design Healthy, full-term infants were recruited. Overweight and obesity were defined using measured weight and height according to World Health Organization reference data. Associations between cesarean delivery and being overweight or obese were investigated at age 2, 6, and 10 years (n = 1734, 1244, and 1170, respectively) by multivariate logistic regression models adjusted for socioeconomic status, child characteristics, and maternal prepregnancy characteristics. Results Mothers who gave birth by cesarean delivery (∼17%) had a higher mean prepregnancy body mass index (23.7 kg/m2 vs 22.5 kg/m2), greater mean gestational weight gain (15.3 kg vs 14.5 kg), and shorter mean duration of exclusive breastfeeding (3.4 months vs 3.8 months) compared with those who delivered vaginally. The proportion of obese children was greater in the cesarean delivery group compared with the vaginal delivery group at age 2 years (13.6% vs 8.3%), but not at older ages. Regression analyses revealed a greater likelihood of obesity at age 2 years in the cesarean delivery group compared with the vaginal delivery group at age 2 years (aOR, 1.68; 95% CI, 1.10-2.58), but not at age 6 years (aOR, 1.49; 95% CI, 0.55-4.05) or age 10 years (aOR, 1.16; 95% CI, 0.59-2.29). Conclusion Cesarean delivery may increase the risk of obesity in early childhood. Our results do not support the hypothesis that an increasing rate of cesarean delivery contributes to obesity in childhood.
    The Journal of pediatrics 05/2014; · 4.02 Impact Factor
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    ABSTRACT: The function of interleukin-37 is not resolved yet. We recently showed that IL-37 suppresses colonic inflammation in mice. To gain more insight into its relevance in human disease, we investigated the expression of IL-37 in the intestine of pediatric patients with chronic inflammatory bowel disease. Intestinal biopsies were obtained from children with inflammatory bowel disease (18 Crohn's disease (CD), 14 ulcerative colitis (UC) and 11 controls) during endoscopy and analyzed for IL-37 expression by immunohistochemistry and real-time PCR. Results were correlated with immunostaining for IL-18 and IL17, mRNA levels of pro- and anti-inflammatory cytokines and clinical parameters. IL-37 protein was detected in epithelial cells and submucosal lymphoid cells of CD and UC patients as well as healthy controls. IL-37 protein expression tended to be higher with submucosal lymphoid cell infiltration of patients with CD and UC and correlated with histological severity score of inflammation. IL-18 showed a similar staining pattern to IL-37, whereas staining for IL-17 revealed distinct positive cells scattered in the submucosal layer. Messenger RNA-expression of IL-8, IL-17 and IL-10 was up-regulated in CD and UC patients. mRNA-levels of IL-18 and IL-37 were not significantly elevated compared to controls. Levels of IL-37 and IL-18 mRNA showed a positive correlation in the CD group. IL-37 protein is expressed in healthy and diseased bowel tissue. IL-37 and IL-18 show a similar expression pattern and correlate at mRNA levels. Future studies are warranted to delineate the specific contribution of IL-37 to modulate chronic bowel inflammation in humans.
    Journal of pediatric gastroenterology and nutrition 04/2014; · 2.18 Impact Factor
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    ABSTRACT: Background Exclusive enteral nutrition (EEN) induces remission and mucosal healing in children with active Crohn's disease (CD).AimTo compare short- and long-term outcomes of the first vs. second courses of EEN, and to identify predictors of sustained remission.Methods Retrospective single centre analysis of all patients with CD (6–18 years) treated with EEN over 7.5 years. Patients were excluded if exposed to anti-TNFα or corticosteroids 3 months prior to EEN. Data included disease phenotype, activity, NOD2 genotype, laboratory indices and anthropometrics. Remission and relapse were defined by mathematically weighted Paediatric Crohn's Disease Activity Index (wPCDAI) with 1-year follow-up.ResultsOf 94 patients treated with EEN, 52 fulfilled inclusion criteria (31 male, mean age 13.2 years). Azathioprine was started within the first month in 33/52 patients; 26/52 received a second EEN course. First compared to second EEN revealed higher wPCDAI at start (59 vs. 40, P < 0.0001), tended to higher remission rates after 3 months (92% vs. 77%, n.s.), but showed comparable 1-year relapse rates (67% vs. 70%, median time 231 vs. 145 days, n.s.). Disease activity, weight gain and inflammatory markers showed better improvement with first EEN. Faecal calprotectin >200 μg/g during EEN was associated with shorter remission (median time 157 vs. 287 days, n.s.). Certain NOD2 genotypes were related to higher relapse rates (92% R702W or G908R vs. 50% 1007fs vs. 60% wild-type, P < 0.01).Conclusions Exclusive enteral nutrition induces remission in active Crohn's disease, but efficacy tends to decrease with the second course. Despite early azathioprine use, 1-year relapse rates are high, but may be related to NOD2 genotype.
    Alimentary Pharmacology & Therapeutics 04/2014; · 4.55 Impact Factor
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    ABSTRACT: Patient satisfaction is a relevant prognostic factor in young persons with chronic disease and may be both age and disease specific. To assess health care quality from the patient's view in young persons with inflammatory bowel disease, an easy to use, valid, reliable and informative specific instrument was needed. All parts of the study were directed at persons with inflammatory bowel disease aged 15 to 24 ([double low-9 quotation mark]youth"). A qualitative internet patient survey was used to generate items, complemented by a physician survey and literature search. A 2nd internet survey served to reduce items based on perceived importance and representativeness. Following pilot testing to assess ease of use and face validity, 150 respondents to a postal survey in patients from a paediatric clinical registry were included for validation analyses. Construct validity was assessed by relating summary scores to results from global questions on satisfaction with care using ANOVA. To assess test-retest reliability using intraclass correlation coefficients (ICC), a subset of patients were assessed twice within 3 months. 302 persons with IBD and 55 physicians participated in the item generating internet survey, resulting in 3,954 statements. After discarding redundancies 256 statements were presented in the 2nd internet survey. Of these, 32 items were retained. The resulting instrument assesses both the perceived relevance (importance) of an item as well as the performance of the care giver for each item for calculation of a summary satisfaction score (range 0 to 1). Sensibility testing showed good acceptance for most items. Construct validity was good, with mean scores of 0.63 (0.50 to 0.76), 0.71 (0.69 to 0.74) and 0.81 (0.79 to 0.83) for no, some and good global satisfaction (ANOVA, p < 0.001). Test-retest reliability was satisfactory (ICC 0.6 to 0.7). We developed an easy to use, patient oriented, valid instrument to assess satisfaction with care in young persons with IBD for use in survey research.
    BMC Health Services Research 03/2014; 14(1):97. · 1.66 Impact Factor
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    ABSTRACT: Loss-of-function mutations in IL10 and IL10R cause very early onset inflammatory bowel disease (VEO-IBD). Here, we investigated the molecular pathomechanism of a novel intronic IL10RA mutation and describe a new therapeutic approach of T cell replete haploidentical hematopoietic stem cell transplantation (HSCT). Clinical data were collected by chart review. Genotypes of IL10 and IL10R genes were determined by Sanger sequencing. Expression and function of mutated IL-10R1 were assessed by quantitative PCR, Western blot analysis, enzyme-linked immunosorbent assays, confocal microscopy, and flow cytometry. We identified a novel homozygous point mutation in intron 3 of the IL10RA (c.368-10C > G) in three related children with VEO-IBD. Bioinformatical analysis predicted an additional 3' splice site created by the mutation. Quantitative PCR analysis showed normal mRNA expression of mutated IL10RA. Sequencing of the patient's cDNA revealed an insertion of the last nine nucleotides of intron 3 as a result of aberrant splicing. Structure-based modeling suggested misfolding of mutated IL-10R1. Western blot analysis demonstrated a different N-linked glycosylation pattern of mutated protein. Immunofluorescence and FACS analysis revealed impaired expression of mutated IL-10R1 at the plasma membrane. In the absence of HLA-identical donors, T cell replete haploidentical HSCT was successfully performed in two patients. Our findings expand the spectrum of IL10R mutations in VEO-IBD and emphasize the need for genetic diagnosis of mutations in conserved non-coding sequences of candidate genes. Transplantation of haploidentical stem cells represents a curative therapy in IL-10R-deficient patients, but may be complicated by non-engraftment.
    Journal of Clinical Immunology 02/2014; · 2.65 Impact Factor

Publication Stats

5k Citations
1,302.06 Total Impact Points


  • 1998–2014
    • Ludwig-Maximilian-University of Munich
      • • Children in the Department of Surgery, Dr. von Hauner Children's Hospital
      • • Department of Epidemiology
      • • Institute for Strategic Management
      • • Children's Hospital and Children clinic at the Dr. von Hauner Children's Hospital
      München, Bavaria, Germany
  • 2013
    • University of Groningen
      Groningen, Groningen, Netherlands
  • 2008–2013
    • Helmholtz-Zentrum für Umweltforschung
      • Department Umweltimmunologie
      Leipzig, Saxony, Germany
    • St. Marien- und St. Annastiftskrankenhaus
      Ludwigshafen, Rheinland-Pfalz, Germany
  • 2003–2013
    • Marien-Hospital Wesel
      Wesel, North Rhine-Westphalia, Germany
    • Pathologisches Institut Bremerhaven
      Bremerhaven, Bremen, Germany
  • 2012
    • Medical University of Warsaw
      Warszawa, Masovian Voivodeship, Poland
    • Odense University Hospital
      Odense, South Denmark, Denmark
  • 2009–2012
    • Helmholtz Zentrum München
      • Institute of Epidemiology II
      München, Bavaria, Germany
    • University of Wuerzburg
      • Department of Internal Medicine II
      Würzburg, Bavaria, Germany
    • Emory University
      • Department of Pathology and Laboratory Medicine
      Atlanta, GA, United States
  • 1995–2012
    • University Hospital München
      München, Bavaria, Germany
  • 2011
    • Hospital Universitari i Politècnic la Fe
      Valenza, Valencia, Spain
  • 2010
    • Leiden University Medical Centre
      Leyden, South Holland, Netherlands
    • Technische Universität Dresden
      Dresden, Saxony, Germany
  • 2009–2010
    • Technische Universität München
      • Kinderklinik und Poliklinik
      München, Bavaria, Germany
  • 1989–2010
    • University of Toronto
      • • Hospital for Sick Children
      • • Department of Paediatrics
      Toronto, Ontario, Canada
  • 2006
    • University of Southampton
      • Institute of Human Nutrition
      Southampton, ENG, United Kingdom
  • 1983–1993
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1990
    • SickKids
      Toronto, Ontario, Canada