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https://www.readbyqxmd.com/read/28527704/anti-madcam-antibody-pf-00547659-for-ulcerative-colitis-turandot-a-phase-2-randomised-double-blind-placebo-controlled-trial
#1
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
#2
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
#3
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...
May 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28449344/endoscopic-features-and-genetic-background-of-inflammatory-bowel-disease-complicated-with-takayasu-arteritis
#10
Shintaro Akiyama, Toshimitsu Fujii, Katsuyoshi Matsuoka, Ebana Yusuke, Mariko Negi, Kento Takenaka, Masakazu Nagahori, Kazuo Ohtsuka, Mitsuaki Isobe, Mamoru Watanabe
BACKGROUND AND AIM: Takayasu arteritis (TA) is occasionally complicated with inflammatory bowel disease (IBD). This study assessed the endoscopic and genetic features of IBD complicated with TA (IBD-TA). METHODS: This study retrospectively reviewed the clinical charts of 142 TA patients (14 men and 128 women; median age 48.5 years [range, 18-97 years]). Human lymphocyte antigen (HLA) types and a single-nucleotide polymorphism rs6871626 in the IL12B gene were assessed in 101 and 81 patients with TA, respectively...
May 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28442662/possible-involvement-of-mucosal-associated-invariant-t-cells-in-the-progression-of-inflammatory-bowel-diseases
#11
Kentaro Tominaga, Satoshi Yamagiwa, Toru Setsu, Naruhiro Kimura, Hiroki Honda, Hiroteru Kamimura, Yutaka Honda, Masaaki Takamura, Junji Yokoyama, Kenji Suzuki, Toshifumi Wakai, Shuji Terai
Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in anti-bacterial immunity. Recent studies have demonstrated that MAIT cells might be implicated in inflammatory bowel diseases (IBDs), but their precise function in IBD remains to be elucidated. We investigated the possible involvement of MAIT cells in the immunopathogenesis of IBDs. Heparinized peripheral blood and biopsy specimens of the colon were collected from 25 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), and 19 heathy individuals...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28432476/immunological-mechanisms-of-adsorptive-cytapheresis-in-inflammatory-bowel-disease
#12
REVIEW
Esteban Sáez-González, Inés Moret, Diego Alvarez-Sotomayor, Francia Carolina Díaz-Jaime, Elena Cerrillo, Marisa Iborra, Pilar Nos, Belén Beltrán
Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). The study of immunological pathways involved in the onset of IBD is of fundamental importance to identify potential biological markers of disease activity and specific targets for therapy. Removing excess and activated circulating leukocytes with adsorptive cytapheresis has been shown to be a potentially effective treatment for patients with an inflamed bowel. Adsorptive cytapheresis is a non-pharmacological approach for active IBD, in which known sources of inflammatory cytokines such as activated myeloid lineage leucocytes are selectively depleted from the circulatory system...
April 21, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28424989/t-lymphocyte-derived-enkephalins-reduce-th1-th17-colitis-and-associated-pain-in-mice
#13
Lilian Basso, Laure Garnier, Arnaud Bessac, Jérôme Boué, Catherine Blanpied, Nicolas Cenac, Sophie Laffont, Gilles Dietrich
BACKGROUND: Endogenous opioids, including enkephalins, are fundamental regulators of pain. In inflammatory conditions, the local release of opioids by leukocytes at the inflammatory site inhibits nociceptor firing, thereby inducing analgesia. Accordingly, in chronic intestinal Th1/Th17-associated inflammation, enkephalins released by colitogenic CD4(+) T lymphocytes relieve inflammation-induced visceral pain. The present study aims to investigate whether mucosal T-cell-derived enkephalins also exhibit a potent anti-inflammatory activity as described for exogenous opioid drugs in Th1/Th17-associated colitis...
April 19, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28407743/new-drugs-new-toxicities-severe-side-effects-of-modern-targeted-and-immunotherapy-of-cancer-and-their-management
#14
REVIEW
Frank Kroschinsky, Friedrich Stölzel, Simone von Bonin, Gernot Beutel, Matthias Kochanek, Michael Kiehl, Peter Schellongowski
Pharmacological and cellular treatment of cancer is changing dramatically with benefits for patient outcome and comfort, but also with new toxicity profiles. The majority of adverse events can be classified as mild or moderate, but severe and life-threatening complications requiring ICU admission also occur. This review will focus on pathophysiology, symptoms, and management of these events based on the available literature.While standard antineoplastic therapy is associated with immunosuppression and infections, some of the recent approaches induce overwhelming inflammation and autoimmunity...
April 14, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28387954/immune-modulator-induced-changes-in-the-gastrointestinal-tract-reply
#15
Raul S Gonzalez, Safia N Salaria, Caitlin D Bohannon, Aaron R Huber, Michael M Feely, Chanjuan Shi
We thank Bavi et al for their response to our article, which includes a series of 34 gastrointestinal biopsies from 21 patients taking a PD-1 or PD-L1 inhibitor. It is not surprising that a sizable minority of their colon cases demonstrated increased intraepithelial lymphocytes; indeed, we considered it somewhat unusual that our cohort generally did not express this finding, given that CTLA-4 inhibitors commonly induce this pattern of injury in humans. Since publication of our series, we have learned of several additional cases of PD-1 inhibitor colitis, some from the literature(1) and others from lecture presentations...
April 7, 2017: Histopathology
https://www.readbyqxmd.com/read/28368458/baseline-gut-microbiota-predicts-clinical-response-and-colitis-in-metastatic-melanoma-patients-treated-with-ipilimumab
#16
N Chaput, P Lepage, C Coutzac, E Soularue, K Le Roux, C Monot, L Boselli, E Routier, L Cassard, M Collins, T Vaysse, L Marthey, A Eggermont, V Asvatourian, E Lanoy, C Mateus, C Robert, F Carbonnel
Background: HASH(0x3bb4818) Ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, prolongs survival in a subset of patients with metastatic melanoma but can induce immune-related adverse events, including enterocolitis. We hypothesized that baseline gut microbiota could predict ipilimumab anti-tumor response and/or intestinal toxicity. Patients and Methods: HASH(0x3bb84b8) Twenty-six patients with metastatic melanoma treated with ipilimumab were prospectively enrolled...
March 27, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28350750/family-history-comorbidity-smoking-and-other-risk-factors-in-microscopic-colitis-a-case-control-study
#17
Anna Wickbom, Nils Nyhlin, Scott M Montgomery, Johan Bohr, Curt Tysk
OBJECTIVES: Data on heredity, risk factors and comorbidity in microscopic colitis, encompassing collagenous colitis (CC) and lymphocytic colitis (LC), are limited. AIM: The aim was to carry out a case-control study of family history, childhood circumstances, educational level, marital status, smoking and comorbidity in microscopic colitis. METHODS: A postal questionnaire was sent in 2008-2009 to microscopic colitis patients resident in Sweden and three population-based controls per patient, matched for age, sex and municipality...
May 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28344807/ipilimumab-induced-thrombotic-thrombocytopenic-purpura-ttp
#18
Jeanelle King, Javier de la Cruz, Jose Lutzky
BACKGROUND: CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) was the first immune checkpoint receptor clinically targeted for use in cancer treatment. It is expressed exclusively on T-cells where its primary role is to regulate the amplitude of the early stages of T-cell activation.1 Ipilimumab, a CTLA-4 blocking antibody, has been widely used for the treatment of patients with high risk and metastatic melanoma. Given its mechanism of action and consequent immune activation, the side effect profile of this drug greatly differs from that of standard cytotoxic chemotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28337881/indoleamine-2-3-dioxygenase-and-regulatory-t-cells-in-intestinal-mucosa-in-children-with-inflammatory-bowel-disease
#19
K Sznurkowska, A Żawrocki, J Sznurkowski, E Iżycka-Świeszewska, P Landowski, A Szlagatys-Sidorkiewicz, K Plata-Nazar, B Kamińska
Impaired immune regulation has been suggested as an underlying mechanism of inflammatory bowel disease. Indoleamine 2,3-dioxygenase (IDO) and regulatory T cells expressing FOXP3 are crucial elements of immune regulation. Conversion of FOXP3- lymphocytes to Tregs is one of the functions of IDO. The aim of this study was to evaluate the number of cells expressing FOXP3 and IDO in the lamina propria of intestinal mucosa and to evaluate correlations between these parameters and disease activity. Sixty-six children newly diagnosed with inflammatory bowel disease (41 patients with ulcerative colitis and 25 patients with Crohn’s disease) were included in the study...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28296676/histopathologic-features-of-colitis-due-to-immunotherapy-with-anti-pd-1-antibodies
#20
Jonathan H Chen, Maryam K Pezhouh, Gregory Y Lauwers, Ricard Masia
Programmed cell death protein 1 (PD-1) blocking agents are novel immunotherapeutics used for treatment of advanced-stage malignancies. They have shown promise in the treatment of several malignancies, with greater efficacy and better tolerability than cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking agents. However, as with anti-CTLA-4 agents, clinically significant colitis remains an important complication. Although there is growing awareness of the histopathologic features of anti-CTLA-4 therapy, there is little information on the pathologic features of anti-PD-1 colitis...
May 2017: American Journal of Surgical Pathology
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