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Objective: Data to support treatment algorithms in ambulatory paediatric UC are scarce. We aimed to explore the 1 year outcome in an inception cohort of paediatric UC patients and to identify early predictors of good outcome that might serve as short term treatment targets., Design: A chart review of 115 children with new onset UC was performed (age 11 ± 4.1 years; 58 (50%) males; 86 (75%) extensive colitis; 70 (61%) moderate-severe disease; 63 (55%) received steroids at baseline). We assessed the Paediatric Ulcerative Colitis Activity Index (PUCAI) and laboratory variables at the time of diagnosis and at 3 months, and endoscopy at diagnosis., Results: The 3 month PUCAI was the strongest predictor of 1 year sustained steroid free remission (SSFR) (area under the receiver operating characteristic curve (AUROC)=0.7 (95% CI 0.6 to 0.8) and colectomy by 2 years (AUROC=0.75 (0.6 to 0.89)). SSFR was achieved in 9/54 (17%) children who had active disease (PUCAI ≥ 10) at 3 months (negative predictive value (NPV)=83%) and by 4/46 (8.6%) of those with a PUCAI score >10; (NPV=91%, positive predictive value=52%; p<0.001), implying that PUCAI >10 at 3 months has a probability of 9% for achieving SSFR versus 48% with a PUCAI value of ≤10. None of the variables at baseline was predictive of SSFR or colectomy (endoscopic severity, disease extent, age, PUCAI or C reactive protein/erythrocyte sedimentation rate/albumin/haemoglobin; all AUROC<0.6, p>0.05) but baseline PUCAI predicted subsequent acute severe colitis and the need for salvage medical therapy., Conclusions: Completeness of the early response appears more important than baseline UC severity for predicting outcome in children, and supports using PUCAI<10 as a feasible treatment goal. Our data suggest that treatment escalation should be considered with a PUCAI value of ≥ 10 at 3 months., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: The NOX2 NADPH oxidase complex produces reactive oxygen species and plays a critical role in the killing of microbes by phagocytes. Genetic mutations in genes encoding components of the complex result in both X-linked and autosomal recessive forms of chronic granulomatous disease (CGD). Patients with CGD often develop intestinal inflammation that is histologically similar to Crohn's colitis, suggesting a common aetiology for both diseases. The aim of this study is to determine if polymorphisms in NOX2 NADPH oxidase complex genes that do not cause CGD are associated with the development of inflammatory bowel disease (IBD)., Methods: Direct sequencing and candidate gene approaches were used to identify susceptibility loci in NADPH oxidase complex genes. Functional studies were carried out on identified variants. Novel findings were replicated in independent cohorts., Results: Sequence analysis identified a novel missense variant in the neutrophil cytosolic factor 2 (NCF2) gene that is associated with very early onset IBD (VEO-IBD) and subsequently found in 4% of patients with VEO-IBD compared with 0.2% of controls (p=1.3×10(-5), OR 23.8 (95% CI 3.9 to 142.5); Fisher exact test). This variant reduced binding of the NCF2 gene product p67(phox) to RAC2. This study found a novel genetic association of RAC2 with Crohn's disease (CD) and replicated the previously reported association of NCF4 with ileal CD., Conclusion: These studies suggest that the rare novel p67(phox) variant results in partial inhibition of oxidase function and are associated with CD in a subgroup of patients with VEO-IBD; and suggest that components of the NADPH oxidase complex are associated with CD.