Identification of chitinase-3-like protein 1 as a novel neutrophil antigenic target in Crohn’s disease

Background and Aims There is an increasing incidence of inflammatory bowel disease [IBD]. Autoimmune responses are involved in the pathophysiology of IBD, but their underlying pathways and target antigens have not yet been fully elucidated. Methods Autoantigenic targets in IBD were identified after separation of whole cell proteins isolated from neutrophils using two-dimensional electrophoresis and matrix assisted laser desorption ionization – time of flight mass spectrometry-based protein identification of the spots that displayed Western blotting signals with anti-neutrophil cytoplasmic antibody-positive sera. The prevalence of IgG, IgA and secretory IgA [sIgA] to chitinase 3-like protein 1 [CHI3L1] was analysed by enzyme-linked immunosorbent assays using recombinant CHI3L1 in 110 patients with Crohn’s disease [CD], 95 with ulcerative colitis [UC], 126 with coeliac disease [CeD] and 86 healthy controls [HCs]. Results The 18-glycosylhydrolase family member CHI3L1 was identified as a neutrophil autoantigenic target. CD patients displayed significantly higher levels of IgG to CHI3L1 than patients with UC and CeD (p < 0.0001, respectively). IgA and sIgA to CHI3L1 was significantly higher in CD than in UC, CeD and HCs [p < 0.0001, respectively]. IgA and sIgA to CHI3L1 demonstrated the highest prevalence in CD [25.5%, 28/110; and 41.8%%, 46/110] compared to HCs [2.3%, 2/86; and 4.7%%, 4/86; p = 0.0015 and p < 0.0001] and are associated with a more complicated progression of CD. Conclusion CHI3L1 is a novel neutrophil autoantigenic target in CD. IgA and sIgA to CHI3L1 may serve as novel markers for CD and may facilitate the serological diagnosis of IBD

School-related experience and performance with inflammatory bowel disease: results from a cross-sectional survey in 675 children and their parents

Objective We describe school performance and experience in children with inflammatory bowel disease (IBD) across Germany and Austria. Predictors of compromised performance and satisfaction were evaluated to identify subgroups of increased risk. Design This cross-sectional analysis was based on a postal survey in children aged 10-15 with Crohn's disease, ulcerative colitis or unclassified IBD and their families. Multivariate regression analysis was used to assess influential factors on parental satisfaction with school, attending advanced secondary education (ASE), having good marks and having to repeat a class. Satisfaction was assessed based on the Child Healthcare-Satisfaction, Utilisation and Needs instrument (possible range 1.00-5.00). Results Of 1367 families contacted, 675 participated in the study (49.4%). Sixty-eight participants (10.2%) had repeated a year, 312 (46.2%) attended ASE. The median school satisfaction score was 2.67 (IQR 2.00-3.33). High socioeconomic status (SES) and region within Germany were predictive for ASE (OR high SES 8.2, 95% CI 4.7 to 14.2). SES, female sex and region of residence predicted good marks. Grade retention was associated with an active disease course (OR 2.7, 95% CI 1.4 to 5.3) and prolonged periods off school due to IBD (OR 3.9, 95% CI 1.8 to 8.6). Conclusions A severe disease course impacted on the risk of grade retention, but not on type of school attended and school marks. Low satisfaction of parents of chronically ill children with the school situation underlines the need for a more interdisciplinary approach in health services and health services research in young people

Orbital inflammation and colitis in pediatric IgG4-related disease: A case report and review of the literature.

IgG4-related disease (IgG4-RD) is an inflammatory disorder characterized by tumor-like swelling in one or more organs, elevated serum IgG4 levels, and histological alterations with infiltration of IgG4-positive plasma cells. IgG4-RD is rare and likely underdiagnosed in children. We report a case of a 16-year-old girl with IgG4-positive colitis that developed weeks after IgG4-related ophthalmic disease and discuss diagnosis and treatment in the context of the literature available. Since the pathophysiology of IgG4-RD is unknown, treatment options are empiric and, for the most part, untargeted. Systemic corticosteroid treatment is the basis of anti-inflammatory treatment in IgG4-RD and induced early remission in our patient. During corticosteroid taper, the patient developed weight loss and intestinal inflammation. Histopathological assessment of the intestinal walls confirmed IgG4-positive colitis. Immune-modulating treatment with non-biologic (e.g., methotrexate (MTX) and mycophenolate mofetil) or biologic (rituximab) disease-modifying antirheumatic drugs has been reported in treatment refractory or corticosteroid-dependent patients. The patient responded to treatment with anti-inflammatory therapy with food rich in TGF-β2 (modulen) and MTX. This is one of the first pediatric patients reported with IgG4-related colitis extending the phenotype of pediatric IgG4-RD. International collaboration to prospectively document clinical presentation and treatment responses may help to further establish the phenotype and treatment options and to raise awareness for IgG4-RD

Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype

Introduction: Zymogen granule glycoprotein 2 (GP2) was demonstrated as first autoimmune mucosal target in primary sclerosing cholangitis (PSC) associated with disease severity. Autoantibodies to four GP2 isoforms (aGP21−4) were found in patients with inflammatory bowel diseases but reactivity against specific GP2 epitopes has not been investigated in PSC yet. Hence, the prevalence of aGP21−4 and their association with the PSC phenotype for risk prediction were examined.Methods: GP2 isoforms were stably expressed as glycosylphosphatidyl - inositol-anchored molecules in the membrane of HEp-2 cells and used as autoantigenic targets in indirect immunofluorescence assay (IFA). aGP21−4 IgA and IgG were detected by IFA in 212 PSC patients of four European university hospitals and 145 controls comprising 95 patients with cystic fibrosis and 50 healthy subjects.Results: Combined aGP21 and aGP24 IgA testing with a sensitivity of 66.0% and a specificity of 97.9% resulted in the best diagnostic performance (Youden index: 0.64) regarding all aGP2 and combinations thereof. aGP24 IgA positivity is significantly associated with the presence of cirrhosis in PSC (p = 0.0056). Logistic regression revealed the occurrence of aGP21 IgA (odds ratio [OR] 1.38, 95% confidence interval [CI]: 1.03–1.86) and aGP24 IgA (OR 1.52, 95%CI: 1.07–2.15) along with male gender (OR 0.51, 95%CI: 0.27–0.97) and older age (OR 1.03 95%CI: 1.01–1.05) as significant risks for the concomitant presence of cirrhosis in PSC.Conclusions: Combined aGP21 and aGP24 IgA analysis is preferred to single aGP2 isoform analysis for sensitive PSC autoantibody testing. Positivity for aGP21 and aGP24 IgA is associated with cirrhosis in PSC and could be used for risk stratification

At the bottom of the differential diagnosis list: unusual causes of pediatric hypertension

Hypertension affects 1–5% of children and adolescents, and the incidence has been increasing in association with obesity. However, secondary causes of hypertension such as renal parenchymal diseases, congenital abnormalities and renovascular disorders still remain the leading cause of pediatric hypertension, particularly in children under 12 years old. Other less common causes of hypertension in children and adolescents, including immobilization, burns, illicit and prescription drugs, dietary supplements, genetic disorders, and tumors will be addressed in this review

Transition from pediatric to adult medical care – A survey in young persons with inflammatory bowel disease

BACKGROUND: Transition to adult health services is a vulnerable phase in young persons with chronic disease. We describe how young persons with inflammatory bowel disease in Germany and Austria experience care during the transitional age, focusing on differences by type of provider (pediatric vs. adult specialist, no specialist). METHODS: This was a follow up survey in patients previously registered with a pediatric IBD registry. Patients aged 15 to 25 received a postal questionnaire, including a measure of health care experience and satisfaction. Descriptive analyses were stratified by age. Sub-analyses in the 18–20 year age group compared health care experience by type of provider. Determinants of early or late transfer were examined using multinomial logistic regression. RESULTS: 619 patients responded to the survey; 605 questionnaires were available for analysis. Usual age of completing transition was 18. Earlier transfer was more common with low parental SES (OR 1.8, 95% CI 0.7 to 4.6), and less common with advanced schooling (OR 0.5, 95% CI 0.2 to 1.2). Structured transition was uncommon. 48% of the respondents had not received any preceding transition advice. Overall satisfaction with IBD care was high, especially with respect to interpersonal aspects, but less so in aspects of continuity of care. CONCLUSIONS: Despite high overall patient satisfaction, relevant deficiencies in transitional care were documented. Some of these were associated with lower parental social status. Differences in health care satisfaction by type of provider (adult vs. pediatric) were small

Metamizole-induced agranulocytosis (MIA): a mini review

Abstract Metamizole is an analgesic, antipyretic, and spasmolytic drug in Germany only approved for the treatment of severe pain or high fever that does not respond to other measures. In recent years, an increased use has been described among both adults and children, often against the approved indication. The most important side effect of metamizole is the development of agranulocytosis (neutrophil count < 500/µL). Incidence of metamizole-induced agranulocytosis (MIA) ranges depending on the study from 0.96 cases per million per year to 1:1602 per patient and metamizole prescription. The risk of agranulocytosis in children remains unclear, but is probably lower than in adults. Female gender and older age are associated with higher incidence, reflecting prescription distribution. MIA is dose-independent and risk seems to increase with duration of intake. In patients with past exposure, re-exposure may lead to rapid onset. MIA is believed to be induced either through immunologic or toxic mechanisms. MIA presents with fever, sore throat, fatigue, and mucosal inflammation, up to ulceration. Even in the case of suspected MIA, treatment with metamizole should be immediately paused and an examination of the blood cell count is required. In case of local or systemic infections, empirical therapy with broad-spectrum antibiotics should be administered. G-CSF therapy should be limited to patients with poor prognostic factors. The patient should be monitored closely until the neutrophil count returns to normal. Re-exposure to metamizole must be avoided

Zöliakieprävalenz bei Kindern und Jugendlichen in Deutschland

Hintergrund: Eine nicht behandelte Zöliakie geht mit erhöhter Morbidität und Mortalität einher. Für Kinder und Jugendliche in Deutschland gibt es keine aktuellen Zahlen zur Prävalenz der Zöliakie und zum Anteil nicht erkannter Zöliakiepatienten. Methoden: Serumproben von Teilnehmenden der 2003 bis 2006 durchgeführten Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland (KiGGS) wurden auf zöliakiespezifische Autoantikörper und Gesamt-IgA untersucht, um die Prävalenz der Zöliakie abzuschätzen. Ergebnisse: Von 12 741 Studienteilnehmenden im Alter von 1 bis 17 Jahren (6 546 Jungen, 6 195 Mädchen) wurde bei 9 (0,07 %) eine Zöliakie anamnestisch angegeben. Bei 91 Kindern mit normaler IgA-Konzentration und 7 mit IgA-Mangel wurden erhöhte Autoantikörper gegen Gewebetransglutaminase nachgewiesen. Die Prävalenz der unerkannten Zöliakie, geschätzt auf der Basis positiver Autoantikörper, betrug 0,8 % (95-%-Konfidenzintervall [KI]: 0,6–1,0), die Gesamtprävalenz 0,9 %. Seropositive Kinder und Jugendliche hatten im Vergleich zu seronegativen niedrigere Ferritin- und Folsäurewerte und waren bezogen auf alters- und geschlechtsstandardisierte z-Scores tendenziell leichter und kleiner. Schlussfolgerung: Die Zöliakieprävalenz (serologisch und anamnestisch) von 0,9 % in Deutschland ist vergleichbar mit anderen europäischen Ländern und Nordamerika. Kinderärzte, Allgemeinmediziner, Internisten und andere Fachkollegen sollten das breite Spektrum der klinischen Manifestationen kennen. Kinder mit auf Zöliakie verdächtigen Symptomen und/oder solche, die zu einer Risikogruppe gehören, sollten auf Antikörper gegen Gewebetransglutaminase getestet werden; dies gilt auch für symptomatische Erwachsene nach Ausschluss anderer Ursachen. Ob asymptomatische Erwachsene aus Risikogruppen getestet werden sollen, ist noch nicht abschließend diskutiert

Prevalence of Anemia in Pediatric IBD Patients and Impact on Disease Severity: Results of the Pediatric IBD-Registry CEDATA-GPGE®

Aim. To determine the prevalence of anemia and its association with disease severity in children and adolescents with IBD. Methods. CEDATA-GPGE is a registry for pediatric patients with IBD in Germany and Austria from 90 specialized centers. As markers of disease severity, analysis included patient self-assessment on a Likert scale (1–5; 1 = very good) and physicians’ general assessment (0 = no activity to 4 = severe disease) and the disease indices. Anemia was defined as hemoglobin concentration below the 3rd percentile. Results. Prevalence of anemia was 65.2% in CD and 60.2% in UC. Anemic CD and UC patients showed significantly worse self-assessment than patients without anemia (average ± standard deviation; CD: 3.0 ± 0.9 versus 2.5 ± 0.9, p<0.0001; UC: 2.9 ± 0.9 versus 2.3 ± 0.9, p<0.0001). Accordingly, physicians’ general assessment (PGA) was significantly worse in anemic than in nonanemic patients in CD (p<0.0001) and UC (p<0.0001). PCDAI in anemic CD, p<0.0001, and PUCAI in anemic UC patients, p<0.0001, were significantly higher than in nonanemic patients. 40.0% of anemic CD and 47.8% of anemic UC patients received iron during follow-up. Conclusion. Almost 2/3 of pediatric IBD patients are anemic. Patients’ self-assessment and disease severity as determined by PGA and activity indices are worse in anemic patients. Contrastingly, only a minority received iron therapy