Immunoglobulin A Glycosylation Differs between Crohn’s Disease and Ulcerative Colitis

Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammations of the digestive tract with increasing prevalence, yet they have unknown origins or cure. CD and UC have similar symptoms but respond differently to surgery and medication. Current diagnostic tools often involve invasive procedures, while laboratory markers for patient stratification are lacking. Large glycomic studies of immunoglobulin G and total plasma glycosylation have shown biomarker potential in IBD and could help determine disease mechanisms and therapeutic treatment choice. Hitherto, the glycosylation signatures of plasma immunoglobulin A, an important immunoglobulin secreted into the intestinal mucin, have remained undetermined in the context of IBD. Our study investigated the associations of immunoglobulin A1 and A2 glycosylation with IBD in 442 IBD cases (188 CD and 254 UC) and 120 healthy controls by reversed-phase liquid chromatography electrospray-ionization mass spectrometry of tryptic glycopeptides. Differences of IgA O- and N-glycosylation (including galactosylation, bisection, sialylation, and antennarity) between patient groups were associated with the diseases, and these findings led to the construction of a statistical model to predict the disease group of the patients without the need of invasive procedures. This study expands the current knowledge about CD and UC and could help in the development of noninvasive biomarkers and better patient care

Obesity is associated with increased risk of Crohn's disease, but not ulcerative colitis: A pooled analysis of five prospective cohort studies

Background and Aims: It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods: We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs). Results: Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m 2) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I 2 = 0%) compared with normal BMI (18.5 to <25 kg/m 2). Each 5 kg/m 2 increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I 2 = 0%). Similarly, with each 5 kg/m 2 increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I 2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I 2 = 0%). No associations were observed between measures of obesity and risk of UC. Conclusions: In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC

Granulomák előfordulási gyakorisága és szerepe 368 Crohn-beteg gyermekben

Bevezetés: A granulomák kulcsszerepet töltenek be a gyulladásos bélbetegségek diagnosztikájában. Nem tisztázott azonban jelentőségük a Crohn-betegség patogenezisében és klinikai megjelenésében. Célkitűzés: A szerzők célul tűzték ki a granulomák gyakoriságának és jelentőségének meghatározását a Magyar Gyermekkori Gyulladásos Bélbetegség Regiszter alapján. Módszer: 2007. január 1. és 2010. december 31. között 368 Crohn-beteg adatait elemezték. Eredmények: A granulomák gyakorisága a diagnóziskor 31,4% (111/353) volt. A granulomák izolált megjelenése a felső gastrointestinalis rendszerben 2,5%, a terminalis ileumban 5% volt. A granulomás és a nem granulomás csoport között nem volt eltérés a fenotípusban és aktivitási indexben. Az immunmoduláns és a biológiai kezelés gyakorisága hasonló volt a két csoportban. Következtetések: A granulomák gyakorisága hazánkban megegyezik a nemzetközi tapasztalatokkal. Kiemelendő, hogy a terminalis ileumban vagy a felső gastrointestinalis rendszerben izoláltan talált granulomák 13 Crohn-beteg gyermekből egynél járultak hozzá a diagnózis felállításához. Ezek az adatok felhívják a figyelmet arra, hogy a béltraktus minden szegmenséből vett többszörös biopsziás mintavétel a diagnózis felállításához nélkülözhetetlen. Orv. Hetil., 2013, 154, 1702–1708

Patient-reported healthcare expectations in inflammatory bowel diseases.

BACKGROUND: Patient-reported experience is an important component of a holistic approach to quality of care. Patients' expectations of treatments and global disease management may indicate their illness representations and their satisfaction and hopes regarding quality of care. OBJECTIVE: To study expectations of patients with inflammatory bowel disease. METHODS: Two focus groups were conducted with 14 patients to explore their expectations about treatments and disease management. From qualitative content analyses of focus group discussions, we built a 22-item expectations questionnaire that was sent to 1756 patients of the Swiss IBD cohort. Answers were collected on a visual analog scale from 0 to 100, and medians (interquartile range [IQR]) calculated. Factor analysis identified main expectation dimensions, and multivariate analyses were performed to describe associations with patient characteristics. RESULTS: Of 1094 patients (62%) included in the study, 54% were female, 54% had Crohn's disease, 35% had tertiary education, and 72% were employed. Expectation dimensions comprised realistic, predictive, and ideal expectations and were linked to information, communication, daily care, and disease recognition. Half (11 of 22) of the expectations were ranked as very high (median score &gt; 70), the 2 most important being good coordination between general practitioners and specialists (median score: 89, IQR: 71-96) and information on treatment adverse events (89, IQR: 71-96). Women had overall higher levels of expectations than did men. Expectations were not associated with psychosocial measures, except those related to disease recognition, and most of them were highly associated with increased concerns on disease constraints and uncertainty. CONCLUSIONS: Patients have high expectations for information and communication among caregivers, the levels varying by gender and region. Patients also appear to request more active participation in their disease management

Infliximab in young paediatric IBD patients: it is all about the dosing

Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age < 10 years (young patients, YP) and PK data were available. Older IBD patients aged 10–18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 < 10 year; 105 ≥ 10 years). Median age was 8.3 years (IQR 6.9–8.9) in YP compared with 14.3 years (IQR 12.8–15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 μg/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0–12.9) vs. OP; 5.5 mg/kg (IQR 5.0–9.3); p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI − 1.2 to − 1.01); p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56). Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years.What is Known?What is New

Lifestyle factors associated with inflammatory bowel disease: data from the Swiss IBD cohort study

BACKGROUND: Various environmental risk factors have been associated with the pathogenesis of inflammatory bowel disease. In this study we aimed to identify lifestyle factors that affect the onset of Crohn's disease and ulcerative colitis. METHODS: 2294 patients from the Swiss IBD Cohort Study received a questionnaire regarding physical activity, nutritional habits and status of weight. In addition, a control group was formed comprising patients' childhood friends, who grew up in a similar environment. RESULTS: Overall, 1111 questionnaires were returned (response rate: 48.4%). Significantly more patients with inflammatory bowel disease reported no regular practice of sport during childhood and beginning of adulthood compared to the control group (p = 0.0001). No association between intake of refined sugar and onset of inflammatory bowel disease was observed. More patients with Crohn's disease compared to ulcerative colitis and controls suffered from overweight during childhood (12.8% vs. 7.7% and 9.7%, respectively; p = 0.027). CONCLUSIONS: Our study underlines the relevance of environmental factors in the development of inflammatory bowel disease. Our results imply a protective effect of physical activity regarding the onset of inflammatory bowel disease

Adherence to 5-aminosalicylic acid maintenance treatment in young people with ulcerative colitis: a retrospective cohort study in primary care

BACKGROUND: Maintenance treatment with 5-aminosalicylic acid (5-ASA) is recommended in ulcerative colitis (UC), but accurate estimates of discontinuation and adherence in adolescents transitioning to young adulthood are lacking. AIM: To determine rates and risk factors for discontinuation and adherence to oral 5-ASA in adolescents and young adults 1 year following diagnosis of UC. DESIGN AND SETTING: Observational cohort study using the UK Clinical Practice Research Datalink among adolescents and young adults (aged 10-24 years) diagnosed with UC between 1 January 1998 and 1 May 2016. METHOD: Time to oral 5-ASA discontinuation (days) and adherence rates (proportion of days covered) were calculated during the first year of treatment using Kaplan-Meier survival analysis. Cox regression models were built to estimate the impact of sociodemographic and health-related risk factors. RESULTS: Among 607 adolescents and young adults starting oral 5-ASA maintenance treatment, one-quarter (n = 152) discontinued within 1 month and two- thirds (n = 419) within 1 year. Discontinuation was higher among those aged 18-24 years (74%) than younger age groups (61% and 56% in those aged 10-14 and 15-17 years, respectively). Adherence was lower among young adults than adolescents (69% in those aged 18-24 years versus 80% in those aged 10-14 years). Residents in deprived versus affluent postcodes were more likely to discontinue treatment (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] = 1.10 to 1.92). Early corticosteroid use for an acute flare lowered the likelihood of oral 5-ASA discontinuation (aHR 0.68, 95% CI = 0.51 to 0.90). CONCLUSION: The first year of starting long-term therapies in adolescents and young adults diagnosed with UC is a critical window for active follow-up of maintenance treatment, particularly in those aged 18-24 years and those living in deprived postcodes