scholarly journals Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 245
Author(s):  
Mai Yamamoto ◽  
Meera Shanmuganathan ◽  
Lara Hart ◽  
Nikhil Pai ◽  
Philip Britz-McKibbin
Keyword(s):  
Mass Spectrometry ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Urinary Metabolites ◽  
Urine Samples ◽  
Therapeutic Monitoring ◽  
Induction Treatment ◽  
Early Management ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Rates of pediatric Crohn’s disease (CD) and ulcerative colitis (UC) are increasing globally. Differentiation of these inflammatory bowel disease (IBD) subtypes however can be challenging when relying on invasive endoscopic approaches. We sought to identify urinary metabolic signatures of pediatric IBD at diagnosis, and during induction treatment. Nontargeted metabolite profiling of urine samples from CD (n = 18) and UC (n = 8) in a pediatric retrospective cohort study was performed using multisegment injection-capillary electrophoresis-mass spectrometry. Over 122 urinary metabolites were reliably measured from pediatric IBD patients, and unknown metabolites were identified by tandem mass spectrometry. Dynamic changes in sum-normalized urinary metabolites were also monitored following exclusive enteral nutrition (EEN) or corticosteroid therapy (CS) in repeat urine samples collected over 8 weeks. Higher urinary excretion of indoxyl sulfate, hydroxyindoxyl sulfate, phenylacetylglutamine, and sialic acid were measured in CD as compared to UC patients, but lower threonine, serine, kynurenine, and hypoxanthine (p < 0.05). Excellent discrimination of CD from UC was achieved based on the urinary serine:indoxylsulfate ratio (AUC = 0.972; p = 3.21 × 10−5). Urinary octanoyl glucuronide, pantothenic acid, and pyridoxic acid were also identified as specific dietary biomarkers of EEN in pediatric IBD patients who achieved clinical remission. This work may complement or replace existing strategies in the diagnosis and early management of children with IBD.

scholarly journals Profiling of Amino Acids in Urine Samples of Patients Suffering from Inflammatory Bowel Disease by Capillary Electrophoresis-Mass Spectrometry

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3345 ◽  
Author(s):  
Juraj Piestansky ◽  
Dominika Olesova ◽  
Jaroslav Galba ◽  
Katarina Marakova ◽  
Vojtech Parrak ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Inflammatory Bowel Disease ◽  
Capillary Electrophoresis ◽  
Amino Acid ◽  
Bowel Disease ◽  
Urine Samples ◽  
Simultaneous Action ◽  
Relative Standard ◽  
Inflammatory Bowel

Urine represents a convenient biofluid for metabolomic studies due to its noninvasive collection and richness in metabolites. Here, amino acids are valuable biomarkers for their ability to reflect imbalances of different biochemical pathways. An impact of amino acids on pathology, prognosis and therapy of various diseases, including inflammatory bowel disease (IBD), is therefore the subject of current clinical research. This work is aimed to develop a capillary electrophoresis-tandem mass spectrometry (CE-MS/MS) method for the quantification of the 20 proteinogenic amino acids in human urine samples obtained from patients suffering from IBD and treated with thiopurines. The optimized CE-MS/MS method, with minimum sample preparation (just “dilute and shoot”), exhibited excellent linearity for all the analytes (coefficients of determination were higher than 0.99), with inter-day and intra-day precision yielding relative standard deviations in the range of 0.91–15.12% and with accuracy yielding relative errors in the range of 85.47–112.46%. Total analysis time, an important parameter for the sample throughput demanded in routine practice, was shorter in ca. 17% when compared to established CE-MS methods. Favorable performance of the proposed CE-MS/MS method was also confirmed by the comparison with corresponding ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) method. Consistent data for the investigated amino acid metabolome were obtained using both methods. For the first time, the amino acid profiling by CE-MS approach was applied on the clinical IBD samples. Here, significant differences observed in the concentration levels of some amino acids between IBD patients undergoing thiopurine treatment and healthy volunteers could result from the simultaneous action of the disease and the corresponding therapy. These findings indicate that amino acids analysis could be a valuable tool for the study of mechanism of the IBD treatment by thiopurines.

Phenotypic Features and Longterm Outcomes of Pediatric Inflammatory Bowel Disease Patients with Arthritis and Arthralgia

2017 ◽  
Vol 44 (11) ◽  
pp. 1636-1643 ◽  
Author(s):  
Osnat Nir ◽  
Firas Rinawi ◽  
Gil Amarilyo ◽  
Liora Harel ◽  
Raanan Shamir ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Medical Records ◽  
Biologic Therapy ◽  
Joint Involvement ◽  
Pediatric Inflammatory Bowel Disease ◽  
History Of ◽  
Inflammatory Bowel ◽  
Phenotypic Features ◽  
Pediatric Ibd

Objective.The natural history of pediatric inflammatory bowel disease (IBD) patients with joint involvement has not been clearly described. Thus, we aimed to investigate phenotypic features and clinical outcomes of this distinct association.Methods.The medical records of patients with pediatric IBD diagnosed from 2000 to 2016 were reviewed retrospectively. Main outcome measures included time to first flare, hospitalization, surgery, and biologic therapy.Results.Of 301 patients with Crohn disease (median age 14.2 yrs), 37 (12.3%) had arthritis while 44 (14.6%) had arthralgia at diagnosis. Arthritis and arthralgia were more common in women (p = 0.028). Patients with arthritis and arthralgia demonstrated lower rates of perianal disease (2.7% and 4.5% vs 16.9%, p = 0.013), whereas patients with arthritis were more likely to be treated with biologic therapy (HR 2.05, 95% CI 1.27–3.33, p = 0.009). Of 129 patients with ulcerative colitis (UC; median age 13.7 yrs), 3 (2.3%) had arthritis and 16 (12.4%) had arthralgia at diagnosis. Patients with arthralgia were treated more often with corticosteroids (p = 0.03) or immunomodulator therapies (p = 0.003) compared with those without joint involvement. The likelihood to undergo colectomy was significantly higher in patients with arthralgia (HR 2.9, 95% CI 1.1–7.4, p = 0.04). During followup (median 9.0 yrs), 13 patients developed arthritis (3.3%). Arthralgia at diagnosis was a significant predictor for the development of arthritis during followup (HR 9.0, 95% CI 2.86–28.5, p < 0.001).Conclusion.Pediatric IBD patients with arthritis have distinct phenotypic features. Arthralgia at diagnosis is a predictor for colectomy in UC and a risk factor for the development of arthritis during followup.

scholarly journals Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

2020 ◽  
Vol 21 (9) ◽  
pp. 3364 ◽  
Author(s):  
Sara Salvador-Martín ◽  
Irene Raposo-Gutiérrez ◽  
Víctor Manuel Navas-López ◽  
Carmen Gallego-Fernández ◽  
Ana Moreno-Álvarez ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Expression Profiles ◽  
Statistical Significance ◽  
Early Response ◽  
Response To Treatment ◽  
P Value ◽  
Infliximab Treatment ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.

scholarly journals Trends in Early Outpatient Drug Therapy in Pediatric Inflammatory Bowel Disease in Finland: A Nationwide Register-Based Study in 1999–2009

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Lauri J. Virta ◽  
Kaija-Leena Kolho
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Drug Therapy ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Early Years ◽  
Aminosalicylic Acid ◽  
Pediatric Inflammatory Bowel Disease ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Objective. There are limited data on the changes of treatment strategies of disease-modifying drugs used to treat pediatric inflammatory bowel disease (IBD). Methods. We utilized data from two national registers: the Drug Reimbursement Register for drug costs (for identifying children with IBD) and the Drug Purchase Register (for exposure to drugs), both of which are maintained by the Social Insurance Institution of Finland. The frequencies and trends of drug therapy strategies during the first year of pediatric IBD were evaluated between 1999 and 2009. Results. A total of 481 children diagnosed with IBD were identified. During the first six months, 68% of the patients purchased systemic corticosteroids; these combined with 5-aminosalicylic acid in almost all cases. The use of corticosteroids was stable from the early years compared with the end of the study period. In Crohn's disease, there was a trend towards more active use of azathioprine: the therapy was introduced earlier and proportion of pediatric patients purchasing azathioprine increased by up to 51% (P<0.05). Conclusions. In pediatric IBD, the majority of patients purchased corticosteroid within the first six months, reflecting moderate-to-severe disease. During recent years in pediatric Crohn's disease, the therapeutic strategies of oral medication have changed towards more active immunosuppression with azathioprine.

scholarly journals The Emerging Role of Noncoding RNAs in Pediatric Inflammatory Bowel Disease

2020 ◽  
Vol 26 (7) ◽  
pp. 985-993 ◽  
Author(s):  
Petr Jabandziev ◽  
Julia Bohosova ◽  
Tereza Pinkasova ◽  
Lumir Kunovsky ◽  
Ondrej Slaby ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Expression Profiles ◽  
Significant Proportion ◽  
Noncoding Rnas ◽  
Inflammatory Disorder ◽  
Altered Expression ◽  
Clinical Biomarkers ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Abstract Prevalence of inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gut, has been on the rise in recent years—not only in the adult population but also especially in pediatric patients. Despite the absence of curative treatments, current therapeutic options are able to achieve long-term remission in a significant proportion of cases. To this end, however, there is a need for biomarkers enabling accurate diagnosis, prognosis, and prediction of response to therapies to facilitate a more individualized approach to pediatric IBD patients. In recent years, evidence has continued to evolve concerning noncoding RNAs (ncRNAs) and their roles as integral factors in key immune-related cellular pathways. Specific deregulation patterns of ncRNAs have been linked to pathogenesis of various diseases, including pediatric IBD. In this article, we provide an overview of current knowledge on ncRNAs, their altered expression profiles in pediatric IBD patients, and how these are emerging as potentially valuable clinical biomarkers as we enter an era of personalized medicine.

scholarly journals P021 Circulating inflammatory protein and cellular profiles at time of diagnosis classify inflammatory bowel disease patients according to their underlying immune response and clinical disease course

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S139-S139
Author(s):  
M Heredia ◽  
M Charrout ◽  
R Klomberg ◽  
M Aardoom ◽  
M Jongsma ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Interferon Γ ◽  
Clinical Disease ◽  
Protein Abundance ◽  
Th Cells ◽  
Inflammatory Protein ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Abstract Background Chronicity of inflammatory bowel disease (IBD) is driven by reactivation of inflammatory memory CD4+ T helper (Th) cells which activate an inflammatory cascade involving innate immune cells and structural intestinal tissue cells. Because of disease heterogeneity, novel treatment strategies tailored to more precisely target the patient’s individual immune defect are required to prevent disease reactivation. We hypothesize that analysis of changes in circulating inflammatory protein abundance combined with phenotyping of circulating Th cells allow to dissect underlying immune pathogenesis and we aim to stratify pediatric IBD patients accordingly. Methods We performed plasma analysis of 92 inflammatory proteins in a cohort of pediatric IBD patients (CD: n=62; UC/IBD-U: n=20), patients with suspicion of IBD but negative diagnosis (n=13) and age-matched healthy controls (HC: n=30). Peripheral blood was obtained at diagnosis and after induction treatment (t=10–14 weeks). Plasma protein concentrations were assessed with Olink Proximity Extension Assay technology® and Th cells were analyzed with flow cytometry. Samples were clustered using hierarchical clustering with Ward linkage. Differential protein abundance was assessed with t-tests at t=0 and a mixed effect model after treatment. Results Thirty-six plasma proteins discriminated pediatric IBD patients from HC. CD and UC/IBD-U patients shared increased abundance of 17 proteins amongst which interleukin-6 and oncostatin-M. Increased abundance of the Th1 cytokine interferon-γ was strictly associated with CD while Th17-associated interleukin-17A was significantly more abundant in UC/IBD-U. Hierarchical clustering of plasma protein profiles discriminated 2 clusters of UC patients with different clinical disease activity and disease extent. In CD, three patient clusters were identified. CD#1 patients had lower clinical disease activity, lower C-reactive protein and higher blood albumin concentrations. Clusters CD#2 and CD#3 had comparable clinical parameters. CD#3 patients had higher abundance of 14 proteins associated with neutrophil function and interferon-γ signaling while CD#2 patients had a marked increase in frequencies of activated (HLA-DR+) memory Th cells. The three CD clusters responded differently to therapy with CD#1 patients exhibiting only a few changes, CD#2 patients showing intermediate modulation and CD#3 patients exhibiting more modulated proteins and greater fold changes. Conclusion Combined plasma immune protein and circulating Th cell profiling discriminates subgroups of pediatric IBD patients during active disease which differ in their response to therapy. Abbreviations: CD: Crohn’s disease; UC: ulcerative colitis; IBD-U: IBD-unclassified.

scholarly journals Incidence and Prevalence Trends of Pediatric Inflammatory Bowel Disease in the Daegu-Kyungpook Province From 2017 to 2020

2022 ◽  
Vol 9 ◽  
Author(s):  
Jae Young Choe ◽  
Sujin Choi ◽  
Ki Hwan Song ◽  
Hyo-Jeong Jang ◽  
Kwang-Hae Choi ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Children And Adolescents ◽  
Bowel Disease ◽  
Population Based ◽  
Annual Number ◽  
Number Of Children ◽  
Pediatric Inflammatory Bowel Disease ◽  
Prevalence Trends ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Background and Aim: There is paucity of data regarding the epidemiology of pediatric IBD in Asia compared to that of Western countries. We aimed to investigate the incidence and prevalence trends of pediatric inflammatory bowel disease (IBD) in the Daegu-Kyungpook province of South Korea from 2017 to 2020.Methods: This study was a multicenter, retrospective study conducted in eight IBD referral centers located in the Daegu-Kyungpook province. Children and adolescents of ≤18 years who were initially diagnosed with IBD between 2017 and 2020 were included. The annual number of children and adolescents newly diagnosed with IBD and the annual resident population of children and adolescents ≤18 years of age in the Daegu-Kyungpook province were investigated to calculate the annual incidence and prevalence in the region.Results: A total 304 children and adolescents that had been diagnosed with IBD were included in this study. Among these patients, 71.4% had been diagnosed with Crohn's disease (CD), and 28.6% with ulcerative colitis (UC). The population based annual incidences of IBD from 2017 to 2020 were each 7.24, 6.82, 10.27, and 13.33 per 100,000, respectively (P for trend &lt;0.001), 4.48, 5.26, 7.39, and 9.8 per 100,000, respectively, for CD (P for trend &lt;0.001), and 2.76, 1.56, 2.88, and 3.53 per 100,000, respectively, for UC (P for trend = 0.174).Conclusion: Pediatric IBD, especially CD has significantly increased recently in the Daegu-Kyungpook province. Epidemiology studies from other regions of Asia are required to better elucidate this trend of increase in Asia.

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