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BackgroundRecently published data indicate that the inflammation in Crohn’s disease (CD) may be accompanied by elevated levels of matrix metalloproteinases. AimsThe goals of the present study were the estimation of MMP-3 and -9 concentrations in sera of children with Crohn’s disease, the examination of correlation between the concentrations of MMP-3 and -9 and clinical activity of the disease in the relation to the control group and the evaluation of the utility of MMP-3 and -9 concentration measurements as markers of disease activity.MethodsSerum concentrations of MMP-3 and -9 were estimated in 82 children (45 CD patients divided into severe, moderate and mild subgroups; 37 controls) and correlated with disease activity estimated by the Pediatric Crohn’s Disease Activity Index (PCDAI), CRP, seromucoid and ESR.ResultsMean MMP-3 concentrations were: 2.49 ng/ml (95% CI: 1.76–3.52) for mild, 16.44 ng/ml (95% CI: 10.34–26.15) for moderate, 5.25 ng/ml (95% CI: 2.73–10.11) for severe CD and 1.95 ng/ml (95% CI: 1.53–2.48) for the control group (differences between all three groups were statistically significant; P < 0.001). Median MMP-9 concentrations were: 2.14 ng/ml (95% CI: 0–8.9) for mild, 14.21 ng/ml (95% CI: 4.53–21.48) for moderate, 42.2 ng/ml (95% CI: 5.74–61.27) for severe CD and 1.3 ng/ml (95% CI: 0.7–2.18) for the control group. MMP-9 concentrations in moderate and severe CD differed from the concentrations in mild CD (P = 0.002) and control group (P = 0.0001). MMP-3 concentration significantly correlated with MMP-9, PCDAI and ESR, while MMP-9 concentration significantly positively correlated with MMP-3, PCDAI, and CRP. Diagnostic utilities of the tests were: MMP-3 accuracy 75%, positive likelihood ratio (LR+) = 4.11 and negative likelihood ratio (LR−) = 0.51, sensitivity 56%, specificity 87%, Youden index 0.43; for MMP-9, accuracy 73%, LR+ = 5.14 and LR− = 0.50, sensitivity 56%, specificity 89%, Youden index 0.45; and for CRP, accuracy 74%, LR+ = 8.56 and LR− = 0.54, sensitivity 49%, specificity 94%, Youden index 0.43. ConclusionsMMP-9 serum concentration increasing along with the activity of the disease, exhibiting high specificity and correlating well with the indices of inflammation might be of better usefulness in the prediction of CD activity status in children than MMP-3.

Although limited by the short-time duration and the heterogeneity of the patients included throughout the 19 centers, our study shows a frequency of 8.1% of ulcers and/or erosions in children, occurring mainly in the second decade of life. H. pylori infection and gastrotoxic medications were less frequently implicated than expected.

HAV is both immunogenic and safe in pediatric patients with IBD.

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Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn’s disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10−11 and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components.

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Background and Aims The study investigates the practical utility of whole-blood gene expression profiling to diagnose inflammatory bowel diseases [IBDs]. Methods The discovery cohorts included 102 and 51 paediatric IBD patients and controls, and 95 and 46 adult IBD patients and controls, respectively. The replication cohorts included 447 and 76 paediatric IBD patients and controls, and 271 and 108 adult IBD patients and controls, respectively. In the discovery phase, RNA samples extracted from whole peripheral blood were analysed using RNA-Seq, and the predictive values of selected biomarkers were validated using quantitative polymerase chain reaction [qPCR]. Results In all, 15 differentially expressed transcripts [adjusted p ≤0.05] were selected from the discovery sequencing datasets. The receiver operating characteristic curves and area under the curve [ROC-AUC] in replication analyses showed high discriminative power [AUC range, 0.91–0.98] for 11 mRNAs in paediatric patients with active IBD. By contrast, the AUC-ROC values ranged from 0.63 to 0.75 in comparison among inactive paediatric IBDs and active/inactive adult IBDs, indicating a lack of discriminative power. The best multi-mRNA diagnostic classifier showed moderate discriminative power [AUC = 0.81] for paediatric inactive IBD, but was not able to discriminate active or inactive adult IBD patients from controls. The AUC-ROC values did not confirm an ability of the mRNAs abundances to discriminate between active ulcerative colitis and active Crohn’s disease in paediatric or adult populations. Conclusions This study identifies and validates blood transcriptional biomarkers that could be used in clinical settings as diagnostic predictors of IBD clinical activity in paediatric, but not adult, IBD patients.