Inflammatory bowel disease in Asia: response to therapy

2007 ◽  
pp. 19-21
Author(s):  
Q. Ouyang ◽  
H. Zhang ◽  
Y. Wang ◽  
X. Chen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Response To Therapy ◽  
Inflammatory Bowel

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 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.

scholarly journals Emerging treatments for inflammatory bowel disease

2020 ◽  
Vol 11 ◽  
pp. 204062231989929 ◽  
Author(s):  
Karl Hazel ◽  
Anthony O’Connor
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Severe Disease ◽  
Treatment Options ◽  
Response To Therapy ◽  
Interleukin 12 ◽  
Cell Transplant ◽  
Faecal Microbiota ◽  
Emerging Treatments ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation, a relapsing and remitting clinical course, requirement for lifelong medication and often, significant morbidity. While multiple effective therapeutic options exist for the treatment of IBD, a proportion of patients will either fail to respond or lose response to therapy. Advances in therapeutics, such as the gut-specific anti-integrins, now offer patients an alternative option to systemic immunosuppression. Anti-interleukin 12 (anti-IL-12)/IL-23 agents offer new and effective treatment options for CD, while the oral small molecules now offer an oral alternative for the treatment of moderate-to-severe disease, previously requiring subcutaneous injection or intravenous infusion. Alternatives to pharmacological treatment such as stem-cell transplant and faecal microbiota transplant are also showing some promise in the treatment of both CD and UC.

Are We Ready to Include Prognostic Factors in Inflammatory Bowel Disease Trials?

2019 ◽  
Vol 25 (1) ◽  
pp. 64-68 ◽  
Author(s):  
Christopher R. Lindholm ◽  
Corey A. Siegel
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Bowel Disease ◽  
Clinical Decision Making ◽  
Scoring Systems ◽  
Clinical Decision ◽  
Chronic Inflammatory Disease ◽  
Response To Therapy ◽  
Clinical Activity ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic inflammatory disease characterized by periodic episodes of flares and remission. Treatment is aimed at healing the bowel, to ultimately decrease hospitalization rates, need for surgeries and overall disability. In more recent years, treatment has transitioned from a reactive approach to a more proactive approach focusing on treating disease earlier and preventing complications. The challenge lies in identifying patients who need more intensive treatment early and trying to determine who will respond to which medications. Biomarkers and clinical activity scoring systems can be used to help guide treatment decisions. However, IBDs are very heterogeneous and the significance of these biomarkers can be difficult to discern on an individual basis. Recently, prognostic tools have been developed to aid in determining a patient’s prognosis as well as their likelihood to respond to different therapies. Despite this progress, clinical trials have not routinely adopted this approach in their study design. Tools for stratification of disease severity and to personalize treatment choices have the potential to improve our studies both by enriching the patient population and further guiding clinical decision making in practice. This review aims to discuss biomarkers, current prognosticating tools, tools that determine response to therapy and how incorporating these into clinical trials will be beneficial.

Features of very early-onset inflammatory bowel disease: the experience of the Federal Pediatric Center

2021 ◽  
Vol 19 (3) ◽  
pp. 5-13
Author(s):  
P.V. Shumilov ◽  
◽  
A.E. Shchigoleva ◽  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Primary Immunodeficiency ◽  
Bowel Disease ◽  
Early Onset ◽  
Activity Index ◽  
Response To Therapy ◽  
Inflammatory Bowel

Objective. To clarify the incidence of monogenic IBD-like diseases and the features of clinical course and response to therapy of major types of inflammatory bowel diseases (IBD) among children under the age of 6 with manifestation of the disease. Patients and methods. The study included 135 children under the age of 6 with manifestation of IBD; in the comparison group, there were 128 children after the age of 6 with manifestation of IBD (97 children with ulcerative colitis (UC) and 31 children with Crohn’s disease (CD)) who were observed for at least 1 year. All children underwent a standard examination, including calprotectin and antineutrophil antibodies testing, determination of activity by the Pediatric Ulcerative Colitis Activity Index (PUCAI) or the Pediatric Crohn’s Disease Activity Index (PCDAI), depending on the nosology. Children with the onset of IBD under 6 years of age underwent a genetic testing using Primary Immunodeficiency Panel by next-generation sequencing. All children were analyzed for efficacy of therapy during catamnestic observation. Results. It was revealed that in the study group the incidence of monogenic IBD-like diseases was 6.7%, of UC – 71.1%, of CD – 22.2%. Major types of IBD with very early onset differed little in their clinical, endoscopic and laboratory features from the forms with manifestation at an older age. In most cases, both CD (57%) and UC (71%) were characterized by low activity. Very earlyonset CD was characterized by isolated localization of the colon (53%, p = 0.037) and a non-stenotic and non-penetrating behaviour of the disease (60% of cases). The leading clinical symptoms were diarrhea (67%) and blood in the stool (63%, p = 0.04). Very early-onset UC was characterized by total lesion of the colon (84%, p = 0.001) and the development of anemia (48%, p = 0.01). Among children with very early-onset UC, the percentage of glucocorticosteroid-dependence and glucocorticosteroid-resistance was high, but anti-TNFα therapy was prescribed late. Conclusion. It is advisable to observe children with very early-onset IBD in federal multidisciplinary clinics, where there is experience in managing patients with this pathology. Key words: inflammatory bowel disease, very early onset, Crohn’s disease, ulcerative colitis, primary immunodeficiency, treatment, children

scholarly journals Serologic Markers in Inflammatory Bowel Disease

2006 ◽  
Vol 52 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Xavier Bossuyt
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Young People ◽  
Bowel Disease ◽  
Response To Therapy ◽  
Indeterminate Colitis ◽  
Outer Membrane Porin ◽  
Serologic Markers ◽  
Inflammatory Bowel

Abstract Inflammatory bowel disease (IBD) is an enduring disease involving mostly young people, with symptoms of bloody diarrhea and abdominal cramps. Several antibodies have been associated with IBD, the 2 most comprehensively studied being autoantibodies to neutrophils (atypical perinuclear anti-neutrophil cytoplasmic antibodies) and anti-Saccharomyces cerevisiae antibodies. This review focuses on the value of these antibodies for diagnosing IBD, differentiating Crohn disease from ulcerative colitis, indeterminate colitis, monitoring disease, defining clinical phenotypes, predicting response to therapy, and as subclinical markers. Pancreatic antibodies and newly identified anti-microbial antibodies (anti-outer membrane porin C, anti-I2, and anti-flagellin) are also reviewed.

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.

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