scholarly journals Simultaneous Quantitation of Lipid Biomarkers for Inflammatory Bowel Disease Using LC–MS/MS

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 106
Author(s):  
Yashpal S. Chhonker ◽  
Shrey Kanvinde ◽  
Rizwan Ahmad ◽  
Amar B. Singh ◽  
David Oupický ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Dynamic Range ◽  
Response To Therapy ◽  
Limit Of Quantification ◽  
Highly Sensitive ◽  
The Us ◽  
Healthy Control ◽  
Inflammatory Bowel ◽  
And Oxidative Stress

Eicosanoids are key mediators and regulators of inflammation and oxidative stress that are often used as biomarkers for severity and therapeutic responses in various diseases. We here report a highly sensitive LC-MS/MS method for the simultaneous quantification of at least 66 key eicosanoids in a widely used murine model of colitis. Chromatographic separation was achieved with Shim-Pack XR-ODSIII, 150 × 2.00 mm, 2.2 µm. The mobile phase was operated in gradient conditions and consisted of acetonitrile and 0.1% acetic acid in water with a total flow of 0.37 mL/min. This method is sensitive, with a limit of quantification ranging from 0.01 to 1 ng/mL for the various analytes, has a large dynamic range (200 ng/mL), and a total run time of 25 min. The inter- and intraday accuracy (85–115%), precision (≥85%), and recovery (40–90%) met the acceptance criteria per the US Food and Drug Administration guidelines. This method was successfully applied to evaluate eicosanoid metabolites in mice subjected to colitis versus untreated, healthy control mice. In summary, we developed a highly sensitive and fast LC−MS/MS method that can be used to identify biomarkers for inflammation and potentially help in prognosis of the disease in inflammatory bowel disease (IBD) patients, including the response to therapy.

scholarly journals P019 Colonic mucosal kinase activity, cytokine and chemokine profiles in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S139-S140
Author(s):  
E Brand ◽  
B Roosenboom ◽  
B Malvar Fernandez ◽  
L Lutter ◽  
E van Koolwijk ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Kinase Activity ◽  
Cell Signalling ◽  
Explant Culture ◽  
Janus Kinase ◽  
Oncostatin M ◽  
Healthy Control ◽  
Inflammatory Bowel ◽  
The Difference

Abstract Background With the approval of tofacitinib, an oral Janus Kinase (JAK) inhibitor, modulation of kinase activity has been added to the therapeutic armamentarium of inflammatory bowel disease (IBD). Despite its established efficacy, at least a third of patients will not respond to this or other therapeutic options such as anti-tumour necrosis factor (TNF), anti-interleukin (IL)23/IL12 compounds or vedolizumab. A better understanding of the inflammatory profile could aid in tailoring drugs to individual patients. We therefore explored mucosal cytokine, chemokine and kinase activity profiles in IBD. Methods Colonic mucosal biopsies were collected from (1) patients with Crohn’s disease (CD, N = 8), (2) patients with ulcerative colitis (UC, N = 8) and (3) healthy controls (N = 4). IBD samples were collected both from inflamed and non-inflamed tissue from the same patients. All IBD patients were biological-naïve and had not used corticosteroids in the past 3 months. Biopsies were snap frozen for later kinase activity determination or directly used in a 24-h explant culture. Whole biopsy kinase activity (tyrosine, serine and threonine kinases) was assessed using the Pamgene platform. A 64-analyte panel was examined in the supernatant of the cultured biopsies employing a multiplex assay (Luminex). Results Whole-biopsy kinase activity differed between inflamed and non-inflamed mucosa of IBD patients, with more overall tyrosine kinase activity in inflamed mucosa in UC, and serine/threonine kinase activity in inflamed mucosa in CD as compared with non-inflamed mucosa (Figure 1). The kinase activity profile of non-inflamed mucosa of CD and UC patients was similarly different from mucosa of healthy control participants (Figure 2). The cytokine and chemokine profile of inflamed biopsies differed from non-inflamed IBD biopsies and healthy control biopsies, with higher levels of S100A8, TNFα, IL-6, oncostatin M (OSM) and triggering receptor expressed on myeloid cells-1 (TREM-1), amongst others (Figure 3). Conclusion In IBD, inflammation in the mucosa can be characterised both by explant-culture and kinase activity assessment. The difference in kinase activity between non-inflamed IBD mucosa and healthy control mucosa suggests the presence of sub-clinical alterations in cell signalling. The observed differences in the kinase, cytokine and chemokine profiles underscore the importance of this approach in the elucidation of the pathophysiology in IBD.

scholarly journals OP33 Multi-omics analysis reveals specific bio-geographical and functional characteristics in inflammatory bowel disease intestinal mucosa

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S031-S034
Author(s):  
N Maimon ◽  
S Gerassy-Vainberg ◽  
H Bar-Yosef ◽  
A Alpert ◽  
E Starosvetsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Immune Cell ◽  
Response To Therapy ◽  
Anatomical Location ◽  
Specific Cell ◽  
Cell Composition ◽  
Dominant Feature ◽  
Inflammatory Bowel

Abstract Background Anatomical location and extent of disease are main factors that affect inflammatory bowel disease (IBD) course and prognosis. No explanation is available for segmental intestinal involvement in either Crohn’s disease (CD) or ulcerative colitis (UC), or for selective segmental response to therapy or disease complications. Therefore, studying the cellular composition of different intestinal segments may provide pathophysiological insights into these phenomena. Methods We compared location-specific cell composition and function by Cytometry Time-of-Flight (CyTOF), gene expression and single-cell (sc) RNAseq data obtained from 3 independent cohorts of healthy donors and IBD patients during remission and flare-ups. Using CyTOF data (n = 38 biopsies), we built a high-resolution screening of immune cell behaviour along the intestine. We validated the findings with gene expression data of 370 samples, and expanded screening resolution by computational methodologies. We then tested a specific pathway in scRNAseq data (n = 10 paired biopsies from 5 patients) and validated its significance by cell-specific Significance Analysis of Microarrays (csSAM). Results We found a location along the intestine to be a dominant feature determining immune and non-immune cell composition. We observed that inflammation reduced anatomic segregation beyond cell infiltration, and decreased the ability to cope with oxidative stress. An upregulated IL-6 pathway in T regulatory cells in UC patients was recognised as sigmoid-specific compared with known inflammatory IL-6 roles in macrophages, as seen in the right colon. This observation may be linked to colonic perforations associated with anti-IL-6R treatment. Suppressor of cytokine signalling 3 (SOCS3) may control IL-6 location-specific action. Conclusion Our study displays a unique and comprehensive cell map of IBD in a location-specific context, providing potential explanations to unexplained clinical phenomena. These observations may allow to tailor therapies to affected areas with improved therapeutic index and efficacy.

scholarly journals Prevalence of Inflammatory Bowel Disease in Pediatric and Adult Populations: Recent Estimates From Large National Databases in the United States, 2007–2016

2019 ◽  
Author(s):  
Yizhou Ye ◽  
Sudhakar Manne ◽  
William R Treem ◽  
Dimitri Bennett
Keyword(s):  
United States ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fixed Effects ◽  
Adult Population ◽  
The United States ◽  
Adult Age ◽  
The Us ◽  
Inflammatory Bowel ◽  
National Databases

Abstract Background The latest estimate of the prevalence of inflammatory bowel disease (IBD) in the United States was based on 2009 data, which indicates a need for an up-to-date re-estimation. The objectives of this study were to investigate the prevalence of all forms of IBD including ulcerative colitis (UC), Crohn’s disease (CD), and IBD unspecified (IBDU). Methods Pediatric (age 2–17) and adult (age ≥18) IBD patients were identified from 2 large claims databases. For each year between 2007 and 2016, prevalence was calculated per 100,000 population and standardized based on the 2016 national Census. A fixed-effects meta-analytical model was used for overall prevalence. Results The pediatric prevalence of IBD overall increased by 133%, from 33.0/100,000 in 2007 to 77.0/100,000 in 2016. Among children, CD was twice as prevalent as UC (45.9 vs 21.6). Prevalence was higher in boys than girls for all forms of IBD, in contrast to the adult population where the prevalence was higher in women than men. We also found that the 10–17 age subgroup was the major contributor to the rising pediatric IBD prevalence. For adults, the prevalence of IBD overall increased by 123%, from 214.9 in 2007 to 478.4 in 2016. The prevalence rates of UC and CD were similar (181.1 vs 197.7) in 2016. Conclusions Inflammatory bowel disease continues to affect a substantial proportion of the US population. In 2016, 1 in 209 adults and 1 in 1299 children aged 2–17 were affected by IBD. Prevalence of IBD has been increasing compared with previously published 2009 data.

scholarly journals Prevalence of Joint Hypermobility and Patterns of Articular Manifestations in Patients with Inflammatory Bowel Disease

2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
P. Vounotrypidis ◽  
E. Efremidou ◽  
P. Zezos ◽  
M. Pitiakoudis ◽  
E. Maltezos ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Study Groups ◽  
Joint Hypermobility ◽  
Fisher Exact Test ◽  
Hypermobility Syndrome ◽  
Exact Test ◽  
Significant Difference ◽  
Healthy Control ◽  
Inflammatory Bowel

Objective. The objective is the investigation of Joint Hypermobility (JH) and the Hypermobility Syndrome (HMS) in patients with inflammatory bowel disease (IBD).Methods. We examined 83 patients with IBD and 67 healthy individuals for the presence of JH. Patients were excluded if they were under 18 or over 50 years of age and if they had other conditions which affect joint mobility. Thex2and the Fisher exact test were used appropriately between study groups. Odds ratios (ORs) for the risk of JH and HMS in IBD groups were calculated.Results. A total of 150 individuals (83 IBD patients and 67 healthy controls) participated in the study. 69 IBD patients, 41 with Crohn's Disease (CD) and 28 with ulcerative colitis (UC), were finally eligible. JH was detected in 29 CD patients (70.7%), in 10 UC patients (35.7%), and in 17 healthy control subjects (25.4%). Significant difference was detected on JH in CD patients as compared to UC patients (P=.0063) and controls (P<.0001). The estimated OR for JH was 7.108 (95% CI: 2.98–16.95) in CD and 1.634 (95% CI: 0.63–4.22) in UC patients. HMS was detected in 5 (12.2%) CD and in 1 (3.57%) UC patients. The OR for HMS in CD was 3.75 (95% CI: 0.41–34.007), while 7 (17.1%) CD patients had overlapping symptoms for both HMS and early spondylarthropathy.Conclusions. JH and the HMS are common in CD patients, thus articular manifestations should be carefully interpreted. This implies an involvement of collagen varieties in the pathogenesis of IBD.

scholarly journals Comparison of Real-World Treatment Outcomes With Vedolizumab Versus Infliximab in Biologic-Naive Patients With Inflammatory Bowel Disease

2019 ◽  
Vol 1 (2) ◽  
Author(s):  
Haridarshan Patel ◽  
Dominick Latremouille-Viau ◽  
Rebecca Burne ◽  
Sherry Shi ◽  
Shashi Adsul
Keyword(s):  
Inflammatory Bowel Disease ◽  
Real World ◽  
Bowel Disease ◽  
Treatment Initiation ◽  
Healthcare Resource ◽  
Healthcare Resource Utilization ◽  
Persistence Rates ◽  
The Us ◽  
Inflammatory Bowel

Abstract Background Little is known about long-term real-world effectiveness of vedolizumab versus infliximab in biologic-naive patients with inflammatory bowel disease (IBD). Methods Biologic-naive IBD patients who received vedolizumab or infliximab in the US Explorys Universe database (May 2014–September 2018) were weighted using Entropy-balancing. Results Persistence rates were higher for vedolizumab (N = 542) versus infliximab (N = 1,179) cohort at 12 (84.5% vs 77.5%; P = 0.0061) and 24 (77.6% vs 64.6%; P = 0.0005) months post-maintenance therapy. Healthcare resource utilization composite end point rates were lower in vedolizumab versus infliximab cohort at 12 (36.2% vs 48.2%; P &lt; 0.0001) and 24 (46.9% vs 59.9%; P &lt; 0.0001) months post-treatment initiation. Conclusions Biologic-naive IBD patients who received vedolizumab had better long-term real-world effectiveness measures versus infliximab patients.

scholarly journals Surrogate Fecal Biomarkers in Inflammatory Bowel Disease: Rivals or Complementary Tools of Fecal Calprotectin?

2017 ◽  
Vol 24 (1) ◽  
pp. 78-92 ◽  
Author(s):  
Mirko Di Ruscio ◽  
Filippo Vernia ◽  
Antonio Ciccone ◽  
Giuseppe Frieri ◽  
Giovanni Latella
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Fecal Calprotectin ◽  
Response To Therapy ◽  
Polymorphonuclear Neutrophil ◽  
Cochrane Library ◽  
Clinical Relapse ◽  
Inflammatory Bowel ◽  
Fecal Biomarkers

Abstract Background Current noninvasive methods for assessing intestinal inflammation in inflammatory bowel disease (IBD) remain unsatisfactory. Along with C-reactive protein and erythrocyte sedimentation rate, fecal calprotectin (FC) is the standard test for assessing IBD activity, even though its specificity and accuracy are not optimal and it lacks a validated cutoff. Over the past few decades, several fecal markers released from intestinal inflammatory cells have been investigated in IBD; they are the subject of this systematic review. Methods A systematic electronic search of the English literature up to April 2017 was performed using Medline and the Cochrane Library. Only papers written in English that analyzed fecal biomarkers in IBD were included. In vitro studies, animal studies, studies on blood/serum samples, and studies analyzing FC or fecal lactoferrin alone were excluded. Results Out of 1023 citations, 125 eligible studies were identified. Data were grouped according to each fecal marker including S100A12, high-mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, human neutrophil peptides, neutrophil gelatinase-associated lipocalin, chitinase 3-like-1, matrix metalloproteinase 9, lysozyme, M2-pyruvate kinase, myeloperoxidase, fecal eosinophil proteins, human beta-defensin-2, and beta-glucuronidase. Some of these markers showed a high sensitivity and specificity and correlated with disease activity, response to therapy, and mucosal healing. Furthermore, they showed a potential utility in the prediction of clinical relapse. Conclusions Several fecal biomarkers have the potential to become useful tools complementing FC in IBD diagnosis and monitoring. However, wide variability in their accuracy in assessment of intestinal inflammation suggests the need for further studies.

scholarly journals Clinical Pharmacology of Janus Kinase Inhibitors in Inflammatory Bowel Disease

2020 ◽  
Vol 14 (Supplement_2) ◽  
pp. S725-S736 ◽  
Author(s):  
Pavine L C Lefevre ◽  
Niels Vande Casteele
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Clinical Pharmacology ◽  
Gastrointestinal Tract ◽  
Bowel Disease ◽  
Kinase Inhibitors ◽  
Response To Therapy ◽  
Janus Kinase ◽  
Janus Kinase Inhibitors ◽  
Inflammatory Bowel

Abstract Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, are chronic inflammatory disorders of the gastrointestinal tract which are characterised, in part, by an imbalance in the production of several pro- and anti-inflammatory cytokines. Although various agents are effective for inducing and maintaining remission, approximately 20% of patients are treatment-refractory and require surgery. Parenterally administered monoclonal antibody-based biologics are associated with adverse effects resulting in treatment discontinuation and/or immunogenicity, leading to loss of response to therapy. Approximately 50% of patients who initially respond to treatment with tumour necrosis factor antagonists lose response to therapy within the 1st year of treatment. Incidence of immunogenicity tends to decrease over time, but once present can persist for years, even after treatment discontinuation. Nonimmunogenic oral small molecule therapies, including Janus kinase inhibitors, are currently being developed and have demonstrated efficacy in early phase clinical trials, which has already led to regulatory approval of tofacitinib for the treatment of patients with moderate-to-severe ulcerative colitis. Differentiation of T cells into T helper cells, which are mediators of the inflammatory response in inflammatory bowel disease, is mediated by the Janus kinase signal transducer and activator of the transcription signalling pathway. Absorption and distribution of Janus kinase inhibitors occurs at the site of action in the gastrointestinal tract, and newer compounds are being developed with limited systemic absorption, potentially reducing the risk of adverse effects. The current review describes the clinical pharmacology of approved Janus kinase inhibitors, as well as those in clinical development for the treatment of inflammatory bowel disease.

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