Genetic association and epistatic interaction of the interleukin-10 signaling pathway in pediatric inflammatory bowel disease

To study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD). METHODSA total of 159 pediatric inflammatory IBD patients (Crohn’s disease, n = 136; ulcerative colitis, n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms (SNPs) of the IL-10 gene and the genes IL10RA, IL10RB, STAT3, and HO1, from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease, additive (a) and dominant (d) modeling of SNP interactions was also performed to examine high-order epistasis between combinations of the individual SNPs. RESULTSThe results showed that IL-10 rs304496 was associated with pediatric IBD (P = 0.022), but no association was found for two other IL-10 SNPs, rs1800872 and rs2034498, or for SNPs in genes IL10RA, IL10RB, STAT3, and HO1. However, analysis of epistatic interaction among these genes showed significant interactions: (1) between two IL-10 SNPs rs1800872 and rs3024496 (additive-additive P = 0.00015, Bonferroni P value (Bp) = 0.003); (2) between IL-10RB rs2834167 and HO1 rs2071746 (dominant-additive, P = 0.0018, Bp = 0.039); and (3) among IL-10 rs1800872, IL10RB rs2834167, and HO1 rs2071746 (additive-dominant-additive, P = 0.00015, Bp = 0.005), as well as weak interactions among IL-10 rs1800872, IL-10 rs3024496, and IL-10RA (additive-additive-additive, P = 0.003; Bp = 0.099), and among IL10RA, IL10RB, and HO1 genes (additive-dominant-additive, P = 0.008, Bp = 0.287). CONCLUSIONThese results indicate that both the IL-10 gene itself, and through epistatic interaction with genes within the IL-10/STAT3 signaling pathway, contribute to the risk of pediatric IBD.

Inpatient management of iron deficiency anemia in pediatric patients with inflammatory bowel disease: A single center experience

BACKGROUND Screening for iron deficiency anemia(IDA)is important in managing pediatric patients with inflammatory bowel disease(IBD).Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous(IV)iron to treat IDA in this population.AIM To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our center.METHODS A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019.92 patients met study criteria for IDA,of which 57 received IV iron,17 received oral iron,and 18 were discharged prior to receiving iron therapy.RESULTS Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9(±0.2)g/dL in mean(±SE)hemoglobin(Hb)concentration by the first ambulatory follow-up,compared to patients who received oral iron 0.8(±0.3)g/dL or no iron 0.8(±0.3)g/dL(P=0.03).One out of 57(1.8%)patients that received IV iron therapy experienced an adverse reaction.CONCLUSION Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.

Consensus for criteria of running a pediatric inflammatory bowel disease center using a modified Delphi approach

Background Good quality of care for inflammatory bowel disease(IBD)depends on high-standard management and facility in the IBD center.Yet,there are no clear measures or criteria for evaluating pediatric IBD(PIBD)center in China.The aim of this study was to develop a comprehensive set of quality indicators(QIs)for evaluating PIBD center in China.Methods A modified Delphi consensus-based approach was used to identify a set of QIs of structure,process,and outcomes for defining the criteria.The process included an exhaustive search using complementary approaches to identify potential QIs,and two web-based voting rounds to select the QIs defining the criteria for PIBD center.Results A total of 101 QIs(35 structures,48 processes and 18 outcomes)were included in this consensus.Structure QIs focused on the composition of multidisciplinary team,facilities and services that PIBD center should provide.Process QIs highlight core requirements in diagnosing,evaluating,treating PIBD,and disease follow-up.Outcome QIs mainly included criteria evaluating effectiveness of various interventions in PIBD centers.Conclusion The present Delphi consensus developed a set of main QIs that may be useful for managing a PIBD center.

Inflammatory bowel disease in pediatric and adolescent patients:A biomolecular and histopathological review

Crohn’s disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD) with both overlapping and distinct clinical, pathological and biomolecular features. It has been suggested that pediatric IBD is a distinct disease entity, with probably different disease subtypes.The aim of this study is to review and summarize the evolution of the current concept of pediatric IBD. The results of this review reinforce the idea that pediatric CD and UC may be further classified in various clinicopathologic entities. For clinicians and pathologists convenience, practical algorithms for the distinction of the various subphenotypes of pediatric IBD are also provided.

Comprehensive mutation screening for 10 genes in Chinese patients suffering very early onset inflammatory bowel disease

AIM: To perform sequencing analysis in patients with very early-onset inflammatory bowel disease (VEO-IBD) to determine the genetic basis for VEO-IBD in Chinese pediatric patients. METHODS: A total of 13 Chinese pediatric patients with VEO-IBD were diagnosed from May 2012 and August 2014. The relevant clinical characteristics of these patients were analyzed. Then DNA in the peripheral blood from patients was extracted. Next generation sequencing (NGS) based on an Illumina-Miseq platform was used to analyze the exons in the coding regions of 10 candidate genes: IL-10, IL-10RA, IL-10RB, NOD2, FUT2, IL23R, GPR35, GPR65, TNFSF15, and ADAM30. The Sanger sequencing was used to verify the variations detected in NGS. RESULTS: Out of the 13 pediatric patients, ten were diagnosed with Crohn's disease, and three diagnosed with ulcerative colitis. Mutations in IL-10RA and IL-10RB were detected in five patients. There were four patients who had single nucleotide polymorphisms associated with IBD. Two patients had IL-10RA and FUT2 polymorphisms, and two patients had IL-10RB and FUT2 polymorphisms. Gene variations were not found in the rest four patients. Children with mutations had lower percentile body weight ( 1.0% vs 27.5%, P = 0.002) and hemoglobin ( 87.4 g/L vs 108.5 g/L, P = 0.040) when compared with children without mutations. Although the age of onset was earlier, height was shorter, and the response to treatment was poorer in the mutation group, there was no significant difference in these factors between groups. CONCLUSION: IL-10RA and IL-10RB mutations are common in Chinese children with VEO-IBD. Patients with mutations have an earlier disease onset, lower body weight and hemoglobin, and poorer

Crohn's disease and growth deficiency in children and adolescents

Nutritional concerns, linear growth deficiency, and delayed puberty are currently detected in up to 85% of patients with Crohn's disease(CD) diagnosed at childhood. To provide advice on how to assess and manage nutritional concerns in these patients, a Medline search was conducted using "pediatric inflammatory bowel disease", "pediatric Crohn's disease", "linear growth","pubertal growth", "bone health", and "vitamin D" as key words. Clinical trials, systematic reviews, and metaanalyses published between 2008 and 2013 were selected to produce this narrative review. Studies referring to earlier periods were also considered if the data was relevant to our review. Although current treatment strategies for CD that include anti-tumor necrosis factor-αtherapy have been shown to improve patients' growth rate, linear growth deficiencies are still common. In pediatric CD patients, prolonged diagnostic delay, high initial activity index, and stricturing/penetrating typeof behavior may cause growth deficiencies(in weight and height) and delayed puberty, with several studies reporting that these patients may not reach an optimal bone mass. Glucocorticoids and inflammation inhibit bone formation, though their impact on skeletal modeling remains unclear. Long-term control of active inflammation and an adequate intake of nutrients are both fundamental in promoting normal puberty. Recent evidence suggests that recombinant growth factor therapy is effective in improving short-term linear growth in selected patients, but is of limited benefit for ameliorating mucosal disease and reducing clinical disease activity. The authors conclude that an intense initial treatment(taking a "top-down" approach, with the early introduction of immunomodulatory treatment) may be justified to induce and maintain remission so that the growth of children with CD can catch up, ideally before puberty. Exclusive enteral nutrition has a key role in inducing remission and improving patients' nutritional status.