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Background & Aims Studies are needed to determine the mechanisms of mucosal dysregulation in patients with inflammatory bowel diseases (IBDs) and differences in inflammatory responses of patients with ulcerative colitis (UC) vs Crohn’s disease (CD). We used mass cytometry (CyTOF) to characterize and compare immune cell populations in the mucosa and blood from patients with IBD and without IBD (controls) at single-cell resolution. Methods We performed CyTOF analysis of colonic mucosa samples (n = 87) and peripheral blood mononuclear cells (n = 85) from patients with active or inactive UC or CD and controls. We also performed single-cell RNA sequencing, flow cytometry, and RNA in situ hybridization analyses to validate key findings. We used random forest modeling to identify differences in signatures across subject groups. Results Compared with controls, colonic mucosa samples from patients with IBD had increased abundances of HLA-DR+CD38+ T cells, including T-regulatory cells that produce inflammatory cytokines; CXCR3+ plasmablasts; and IL1B+ macrophages and monocytes. Colonic mucosa samples from patients with UC were characterized by expansion of IL17A+ CD161+ effector memory T cells and IL17A+ T-regulatory cells; expansion of HLA-DR+CD56+ granulocytes; and reductions in type 3 innate lymphoid cells. Mucosal samples from patients with active CD were characterized by IL1B+HLA-DR+CD38+ T cells, IL1B+TNF+IFNG+ naive B cells, IL1B+ dendritic cells (DCs), and IL1B+ plasmacytoid DCs. Peripheral blood mononuclear cells from patients with active CD differed from those of active UC in that the peripheral blood mononuclear cells from patients with CD had increased IL1B+ T-regulatory cells, IL1B+ DCs and IL1B+ plasmacytoid DCs, IL1B+ monocytes, and fewer group 1 innate lymphoid cells. Random forest modeling differentiated active UC from active CD in colonic mucosa and blood samples; top discriminating features included many of the cellular populations identified above. Conclusions We used single-cell technologies to identify immune cell populations specific to mucosa and blood samples from patients with active or inactive CD and UC and controls. This information might be used to develop therapies that target specific cell populations in patients with different types of IBD.

Objective: There is no standardized endoscopic description of upper gastrointestinal [UGI] disease in Crohn's disease [CD]. We prospectively applied the Simple Endoscopic Score for CD [SES-CD] to the UGI tract as a planned sub-study of the multicentre prospective ImageKids study. We aimed to assess the utility of the UGI-SES-CD and its clinical significance in paediatric CD. Design: Patients underwent an oesophagogastroduodenoscopy [EGD], ileocolonoscopy, and magnetic resonance enterography [MRE] with explicit clinical data recorded. SES-CD was scored at each region [oesophagus, stomach body, antrum, and duodenum]. Half of the patients were followed for 18 months, when a repeat MRE was performed. Results: A total of 202 children were included 56% males, mean age 11.5 +/- 3.2 years, median weighted Paediatric Crohn's Disease Activity Index [wPCDAI 25]). UGI-SES-CD score ranged 0-17, with 95 [47%] having a UGI-SES-CD = 1; no narrowing was detected. UGI-SES-CD = 1 was associated with higher: wPCDAI [32.5 vs 20; p = 0.03]; Physician's Global Assessment [PGA] of inflammation (45 mm visual analogue score [VAS] vs 30 mm VAS; p = 0.04); ileocolonoscopic SES-CD [10 vs 7; p = 0.004], faecal calprotectin [717 mu g/g vs 654 mu/g; p= 0.046]; and radiological global assessment of damage by MRE [7 mm VAS vs 0; p = 0.04]. In all, 81 patients were followed for 18 months and no association was identified between initial UGI SES-CD and markers of disease course such as surgery, MRE assessment, or treatment escalation. Conclusion: UGI-SES-CD is an easily reported objective scoring system and is associated with a more severe disease phenotype but not with disease course.

Radiation exposure increases cancer risk in children with Crohn disease (CD). Magnetic resonance enterography (MRE) can image the gastrointestinal tract without exposure to radiation. The aim of the present study was to determine whether our MRE protocol could diagnose terminal ileitis and the degree of inflammatory activity in children with CD.Retrospective review of patients 18 years of age or younger who underwent MRE for known or suspected CD from June 15, 2007 to April 1, 2010. MRE was performed with Volumen and water as oral contrast and gadolinium-based intravenous contrast. No antiperistaltic agent was used. Each MRE was compared with ileal biopsies obtained within 90 days. Severity of inflammation on MRE was scored and compared with the Pediatric Crohn Disease Activity Index (PCDAI).Seventy-two patients underwent 80 MREs during the study period. Forty-two of the 72 patients (58.3%) underwent colonoscopy within 90 days of MRE, and the terminal ileum was intubated in 33. Compared with histology, MRE had a sensitivity of 71.4% and a specificity of 100% for terminal ileitis. The positive and negative predictive values were 100% and 70%, respectively. PCDAI was calculated in 39 of the 72 patients (54.2%) and had a statistically significant positive correlation with MRE score of 0.37 (P = 0.020426).In children with known or suspected CD, our MRE protocol has a high specificity and positive predictive value for terminal ileitis. Severity of inflammation on MRE had a statistically significant positive correlation with PCDAI.

Crohn’s disease is a chronic inflammatory disorder of the GI tract that often presents during childhood and adolescence. Children with Crohn’s disease are often subjected to repeated radiologic examinations throughout the course of their illness, thereby raising great concern over the potential harm of cumulative radiation exposure. Magnetic resonance enterography is a new modality that provides detailed images of the GI tract without exposure to ionizing radiation. This article reviews past methods of bowel imaging, the scope of the problem with regard to radiation exposure, as well as the technical aspects, indications, and current evidence for magnetic resonance enterography in children with Crohn’s disease. Various examples of inflammatory, stricturing and penetrating disease activity are provided.

Objectives The aim of the study was to evaluate infliximab (IFX) dosing and treatment durability relative to luminal disease burden in patients with inflammatory bowel disease. Methods Records from 98 pediatric patients treated with IFX between 2012 and 2014 were reviewed. Disease extent was classified as "limited," "moderate," or "extensive" based on cumulative assessment of mucosal involvement. Patients started taking standard 5 mg/kg dosing were compared with those initiated taking 10 mg/kg with regard to treatment durability. Results Overall, 26.4%, 58.3%, and 70% with limited, moderate, or extensive disease, respectively, started taking a standard IFX dose of 5 mg/kg required therapy escalation. Patients with moderate and extensive disease, started taking the 5 mg/kg per dose, showed statistically significant shorter times to escalation than those with limited disease. The percentage of patients remaining on their initial 5 mg/kg per dose at 12 months was 80.1%, 56.9%, and 40.0% for limited, moderate, and extensive disease, respectively. Among patients started taking 10 mg/kg, 100% remained on this dose. All the patients with limited disease who required dose escalation continued on the higher dose at the time of analysis; however, among those with the most extensive disease, 43% failed escalation because of nonresponse or infusion reaction. Conclusions Patients with extensive disease started taking 5 mg/kg of IFX were more likely to require dose escalation compared to those with limited or moderate disease. All of the patients with moderate and extensive disease started taking 10 mg/kg of IFX remained on this dose. These results suggest that patients with more extensive disease may benefit from higher initial IFX dosing as it relates to durability of the treatment.