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https://www.readbyqxmd.com/read/28626406/late-onset-inflammatory-bowel-disease-like-syndrome-after-ipilimumab-therapy-a-case-report
#1
Reem Akel, Bilal Anouti, Arafat Tfayli
BACKGROUND: Antitumor immunotherapy has become a major player in cancer therapy. Ipilimumab is a humanized monoclonal antibody against the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), an important downregulator of T-cell activation. Ipilimumab has demonstrated tumor regression and improvement in overall survival in patients with metastatic melanoma. Unfortunately, immune activation induced by this drug has been associated with several immune-mediated adverse effects, namely diarrhea and colitis...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28618865/streptococcus-thermophilus-ncimb-41856-ameliorates-signs-of-colitis-in-an-animal-model-of-inflammatory-bowel-disease
#2
J R Bailey, V Vince, N A Williams, T A Cogan
Treatment of inflammatory bowel disease (IBD) is mainly based on suppression of symptoms, often with numerous side effects. Trials of probiotics in IBD have frequently produced disappointing results. The majority of probiotics are unusual, since they do not require iron for growth, unlike many bacteria resident in the intestine. The IBD intestine is iron-rich due to bleeding and use of oral iron supplements; conventional probiotics would be rapidly outcompeted. We have evaluated an iron-responsive Streptococcus thermophilus strain for its potential to reduce signs of colitis...
June 16, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/28614208/il-8-expression-in-granulocytic-epithelial-lesions-of-idiopathic-duct-centric-pancreatitis-type-2-autoimmune-pancreatitis
#3
Yuna Ku, Seung-Mo Hong, Kohei Fujikura, Sung Joo Kim, Masayuki Akita, Shiho Abe-Suzuki, Hideyuki Shiomi, Atsuhiro Masuda, Tomoo Itoh, Takeshi Azuma, Myung-Hwan Kim, Yoh Zen
Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (P<0...
June 13, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28604554/severe-ocular-myositis-after-ipilimumab-treatment-for-melanoma-a-report-of-2-cases
#4
Anna Pushkarevskaya, Ulf Neuberger, Antonia Dimitrakopoulou-Strauss, Alexander Enk, Jessica C Hassel
Ipilimumab binds and blocks cytotoxic T-lymphocyte-associated antigen-4, causing enhanced T-cell reaction, antitumor response, and significant improvement of the overall survival of patients with metastatic melanoma. Patients treated with ipilimumab can develop immune-related adverse effects, primarily dermatitis, colitis, hepatitis, and hypophysitis. Although, in phase I-III studies, 64.2% of all patients suffered from immune-related adverse effects, ocular adverse effects occurred in 1.3% only. In the cases reported below, 2 patients with metastatic melanoma developed severe ocular myositis after treatment with ipilimumab...
June 9, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28597107/microscopic-colitis-evolved-into-inflammatory-bowel-diseases-is-characterized-by-increased-th1-tc1-cells-in-colonic-mucosal-lamina-propria
#5
Ji Li, Yuchu Yan, Ziran Meng, Shuhong Liu, Paul L Beck, Subrata Ghosh, Jiaming Qian, Xianyong Gui
BACKGROUND: An association between microscopic colitis (MC), i.e., lymphocytic colitis (LC) and collagenous colitis (CC), and inflammatory bowel diseases (IBD) has been noticed. A subset of MC cases may evolve into IBD, and IBD in remission may present as MC in a histologic pattern. Moreover, MC and IBD may coexist in different regions of the bowel. A link between MC and IBD in their pathogenesis is, therefore, suggested. Abnormal mucosal immunity is likely the key. METHODS: We reviewed 2324 MC cases in Calgary over 14 years and identified 20 cases evolved into IBD (IBD transformers)...
June 9, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28573508/crossover-subsets-of-cd4-t-lymphocytes-in-the-intestinal-lamina-propria-of%C3%A2-patients-with-crohn-s-disease-and-ulcerative-colitis
#6
Ji Li, Aito Ueno, Marietta Iacucci, Miriam Fort Gasia, Humberto B Jijon, Remo Panaccione, Gilaad G Kaplan, Paul L Beck, Joanne Luider, Herman W Barkema, Jiaming Qian, Xianyong Gui, Subrata Ghosh
BACKGROUND: Hovhannisyan et al. first showed evidence of plasticity between Treg and Th17 in the inflamed intestine of Crohn's disease (CD) patients. Our previous report suggests that the inflammatory cytokine milieu generates IL-17(+) Foxp3(+) CD4(+) T lymphocytes which is a crossover population converting Treg subset to Th17 in the peripheral blood of IBD patients. This is considered as an evidence of Treg/Th17 plasticity. AIM: The aim of this study was to characterize a variety of helper T cell crossover population, not limited to IL-17(+) Foxp3(+) CD4(+) T lymphocytes, in the lamina propria (LP) of IBD patients...
June 1, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28562114/macroscopic-findings-incidence-and-characteristics-of-microscopic-colitis-in-a-large-cohort-of-patients-from-the-united-kingdom
#7
John S Kane, Olorunda Rotimi, Alexander C Ford
OBJECTIVE: Microscopic colitis (MC) is classically associated with normal or near-normal endoscopic appearances. However, non-specific macroscopic findings have been described, the importance of biopsy location for confirming a diagnosis of MC is unclear, and reported incidence data from the United Kingdom are limited. This study was designed to assess macroscopic features, incidence, demographics, and location and positivity of biopsy samples in MC. MATERIALS AND METHODS: Retrospective, cross-sectional study of individuals with newly diagnosed MC...
May 31, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28560327/antibody-mediated-neutralization-of-soluble-mic-significantly-enhances-ctla4-blockade-therapy
#8
Jingyu Zhang, Dai Liu, Guangfu Li, Kevin F Staveley-O'Carroll, Julie N Graff, Zihai Li, Jennifer D Wu
Antibody therapy targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4) elicited survival benefits in cancer patients; however, the overall response rate is limited. In addition, anti-CTLA4 antibody therapy induces a high rate of immune-related adverse events. The underlying factors that may influence anti-CTLA4 antibody therapy are not well defined. We report the impact of a cancer-derived immune modulator, the human-soluble natural killer group 2D (NKG2D) ligand sMIC (soluble major histocompatibility complex I chain-related molecule), on the therapeutic outcome of anti-CTLA4 antibody using an MIC transgenic spontaneous TRAMP (transgenic adenocarcinoma of the mouse prostate)/MIC tumor model...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28548891/immunological-characteristics-of-colitis-associated-with-anti-ctla-4-antibody-therapy
#9
Giorgos Bamias, Ioanna Delladetsima, Marina Perdiki, Spyros I Siakavellas, Dimitrios Goukos, George V Papatheodoridis, George L Daikos, Helen Gogas
Anti-CTL4-A therapy is associated with development of colitis. We characterized ipilimumab-associated colitis in nine melanoma patients (6 male, mean age: 55.3-yrs). Median value for diarrhea grade was 2, number of ipilimumab doses 2, and interval since last administration 3-wks. Endoscopic characteristics resembled inflammatory bowel disease and histology revealed predominance of plasmacytes or CD4+ T-cells. We observed significant upregulation of Th1 and Th17 effector pathways (>10-fold increase for IFN-γmRNA, >5-fold for IL-17A, p < 0...
May 26, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28540290/biomarkers-and-microscopic-colitis-an-unmet-need-in-clinical-practice
#10
REVIEW
Laura Francesca Pisani, Gian Eugenio Tontini, Beatrice Marinoni, Vincenzo Villanacci, Barbara Bruni, Maurizio Vecchi, Luca Pastorelli
One of the most common causes of chronic diarrhea is ascribed to microscopic colitis (MC). MC is classified in subtypes: collagenous colitis (CC) and lymphocytic colitis (LC). Patients with MC report watery, non-bloody diarrhea of chronic course, abdominal pain, weight loss, and fatigue that may impair patient's health-related quality of life. A greater awareness, and concomitantly an increasing number of diagnoses over the last years, has demonstrated that the incidence and prevalence of MC are on the rise...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28533998/ipilimumab-as-a-cause-of-severe-pan-colitis-and-colonic-perforation
#11
Raj Shah, Danielle Witt, Talal Asif, Fahad F Mir
Ipilimumab is a human monoclonal antibody that functions as a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor that is used to treat malignant melanoma. Due to ipilimumab's removal of immune regulation, specifically through the inactivation of CTLA-4, it is commonly associated with inflammatory and autoimmune events. Gastrointestinal (GI) related immune-related adverse events such as diarrhea occur in 29% of patients with 7.6% of patients specifically suffering from colitis. We describe a case of colonic perforation with ipilimumab use...
April 20, 2017: Curēus
https://www.readbyqxmd.com/read/28527704/anti-madcam-antibody-pf-00547659-for-ulcerative-colitis-turandot-a-phase-2-randomised-double-blind-placebo-controlled-trial
#12
Séverine Vermeire, William J Sandborn, Silvio Danese, Xavier Hébuterne, Bruce A Salzberg, Maria Klopocka, Dino Tarabar, Tomas Vanasek, Miloš Greguš, Paul A Hellstern, Joo Sung Kim, Miles P Sparrow, Kenneth J Gorelick, Michelle Hinz, Alaa Ahmad, Vivek Pradhan, Mina Hassan-Zahraee, Robert Clare, Fabio Cataldi, Walter Reinisch
BACKGROUND: PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis. METHODS: This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18-65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy...
May 17, 2017: Lancet
https://www.readbyqxmd.com/read/28523588/advances-in-the-development-of-janus-kinase-inhibitors-in-inflammatory-bowel-disease-future-prospects
#13
Mathurin Flamant, Josselin Rigaill, Stephane Paul, Xavier Roblin
Inflammatory bowel disease (IBD) is caused by a dysregulation of the immune system, inducing the production of proinflammatory cytokines and adhesion molecules. A better understanding of the mucosal immune response in IBD has led to the development of new drugs directed at inflammatory cytokines and leukocyte-trafficking molecules. Beyond tumor necrosis factor antagonists and anti-integrin molecules, which act by blocking the interaction between gut-specific lymphocytes and their receptor on vascular endothelium, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway represents a new target in IBD...
May 18, 2017: Drugs
https://www.readbyqxmd.com/read/28507030/ccr2-regulates-the-immune-response-by-modulating-the-interconversion-and-function-of-effector-and-regulatory-t-cells
#14
Eszter Bakos, Christoph A Thaiss, Matthias P Kramer, Sivan Cohen, Lihi Radomir, Irit Orr, Nathali Kaushansky, Avraham Ben-Nun, Shirly Becker-Herman, Idit Shachar
Chemokines and chemokine receptors establish a complex network modulating immune cell migration and localization. These molecules were also suggested to mediate the differentiation of leukocytes; however, their intrinsic, direct regulation of lymphocyte fate remained unclear. CCR2 is the main chemokine receptor inducing macrophage and monocyte recruitment to sites of inflammation, and it is also expressed on T cells. To assess whether CCR2 directly regulates T cell responses, we followed the fates of CCR2(-/-) T cells in T cell-specific inflammatory models...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28498152/oligoclonal-t-cell-receptor-repertoire-in-colonic-biopsies-of-patients-with-microscopic-colitis-and-ulcerative-colitis
#15
Sezin Günaltay, Dirk Repsilber, Gisela Helenius, Nils Nyhlin, Johan Bohr, Olof Hultgren, Elisabeth Hultgren Hörnquist
BACKGROUND: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology. METHODS: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCRβ) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with noninflamed colons using next-generation sequencing...
May 10, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28489679/ipilimumab-associated-cholestatic-hepatitis-a-case-report-and-literature-review
#16
Sümeyra Yildirim, Kemal Deniz, Ender Doğan, Mevlüt Başkol, Şebnem Gürsoy, Metin Özkan
Ipilimumab is a monoclonal antibody that exerts its effects by inhibiting the cytotoxic T-lymphocyte-associated protein 4 receptor on cytotoxic T lymphocytes. It is frequently used for the treatment of unresectable or metastatic melanoma. Ipilimumab may lead to several immune-related disease including colitis, thyroiditis, pneumonia, hepatitis, or pancreatitis as a side effect. Limited number of cases with hepatic damage as an ipilimumab-related adverse event has been reported in the literature. This agent has been implicated in causing acute hepatitis-like liver injury...
May 5, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28488312/immune-modulator-therapy-for-microscopic-colitis-in-a-case-series-of-73-patients
#17
T G Cotter, A K Kamboj, S B Hicks, W J Tremaine, E V Loftus, D S Pardi
BACKGROUND: Microscopic colitis (MC) is a common cause of chronic diarrhoea. Various treatment options have been described, but there are limited data describing outcomes of corticosteroid-sparing treatments. AIM: To evaluate the outcomes of patients with active MC treated with immune modulators. METHODS: All patients seen at Mayo Clinic, Rochester between January 1, 1997 and November 30, 2016 with a histological diagnosis of MC were identified...
May 10, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28474503/innate-cd8%C3%AE-%C3%AE-lymphocytes-enhance-anti-cd40-antibody-mediated-colitis-in-mice
#18
Aaram A Kumar, Alberto G Delgado, M Blanca Piazuelo, Luc Van Kaer, Danyvid Olivares-Villagómez
INTRODUCTION: Immune responses in the intestines require tight regulation to avoid uncontrolled inflammation. We previously described an innate lymphocyte population in the intestinal epithelium (referred to as innate CD8αα(+) , or iCD8α cells) that can protect against gastrointestinal infections such as those mediated by Citrobacter rodentium. METHODS: Here, we have evaluated the potential contribution of these cells to intestinal inflammation by analyzing inflammation development in mice with decreased numbers of iCD8α cells...
June 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28472424/ven-120-a-recombinant-human-lactoferrin-promotes-a-regulatory-t-cell-treg-phenotype-and-drives-resolution-of-inflammation-in-distinct-murine-models-of-inflammatory-bowel-disease
#19
Christopher F MacManus, Colm B Collins, Tom T Nguyen, Randall W Alfano, Paul Jedlicka, Edwin F de Zoeten
Background and Aims: Inflammatory bowel disease (IBD) is characterized by a disruption of immune homeostasis, which is tightly regulated to protect against harmful pathogens yet not react to commensal antigens. Animal studies indicate that regulatory T cells (Treg) modulate the immune response to prevent IBD development. Lactoferrin (LF), is an endogenous anti-inflammatory pleiotropic protein secreted at high concentrations in colostrum and at mucosal sites. However, the effect of LF on specific T lymphocyte populations has not been studied...
May 2, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28453768/%C3%AE-e%C3%AE-7-integrin-identifies-subsets-of-pro-inflammatory-colonic-cd4-t-lymphocytes-in-ulcerative-colitis
#20
Christopher A Lamb, John C Mansfield, Gaik W Tew, Deena Gibbons, Anna K Long, Peter Irving, Lauri Diehl, Jeff Eastham-Anderson, Maria B Price, Graeme O'Boyle, David E J Jones, Sharon O'Byrne, Adrian Hayday, Mary E Keir, Jackson G Egen, John A Kirby
Background and Aims: The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions of these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, with understanding largely derived from animal model data. Defining this phenotype in human samples is important for understanding UC pathogenesis and is of translational importance for therapeutic targeting of αEβ7-E-cadherin interactions...
May 1, 2017: Journal of Crohn's & Colitis
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