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https://www.readbyqxmd.com/read/28449344/endoscopic-features-and-genetic-background-of-inflammatory-bowel-disease-complicated-with-takayasu-arteritis
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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(0x38685b0) 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(0x4616688) 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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28294127/orai2-modulates-store-operated-calcium-entry-and-t-cell-mediated-immunity
#12
Martin Vaeth, Jun Yang, Megumi Yamashita, Isabelle Zee, Miriam Eckstein, Camille Knosp, Ulrike Kaufmann, Peter Karoly Jani, Rodrigo S Lacruz, Veit Flockerzi, Imre Kacskovics, Murali Prakriya, Stefan Feske
Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels is critical for lymphocyte function and immune responses. CRAC channels are hexamers of ORAI proteins that form the channel pore, but the contributions of individual ORAI homologues to CRAC channel function are not well understood. Here we show that deletion of Orai1 reduces, whereas deletion of Orai2 increases, SOCE in mouse T cells. These distinct effects are due to the ability of ORAI2 to form heteromeric channels with ORAI1 and to attenuate CRAC channel function...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28293233/the-soil-bacterium-methylococcus-capsulatus-bath-interacts-with-human-dendritic-cells-to-modulate-immune-function
#13
Stine Indrelid, Charlotte Kleiveland, René Holst, Morten Jacobsen, Tor Lea
The prevalence of inflammatory bowel disease (IBD) has increased in Western countries during the course of the twentieth century, and is evolving to be a global disease. Recently we showed that a bacterial meal of a non-commensal, non-pathogenic methanotrophic soil bacterium, Methylococcus capsulatus Bath prevents experimentally induced colitis in a murine model of IBD. The mechanism behind the effect has this far not been identified. Here, for the first time we show that M. capsulatus, a soil bacterium adheres specifically to human dendritic cells, influencing DC maturation, cytokine production, and subsequent T cell activation, proliferation and differentiation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28276855/the-safety-of-vedolizumab-for-the-treatment-of-ulcerative-colitis
#14
REVIEW
Gregor Novak, Pieter Hindryckx, Reena Khanna, Vipul Jairath, Brian G Feagan
Vedolizumab is a humanized monoclonal antibody to the α4β7-integrin that blocks lymphocyte trafficking to the gut and is approved for treatment of patients with moderate-to-severe ulcerative colitis (UC). The gut-selective mechanism of action has the potential to improve vedolizumab's safety profile compared to other approved biologic drugs. Areas covered: We review the mechanism of action, efficacy and safety of vedolizumab treatment for UC. The positioning of vedolizumab in management algorithms is also discussed...
April 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28275312/clinical-and-immunologic-effects-of-faecal-microbiota-transplantation-in-a-patient-with-collagenous-colitis
#15
Sezin Günaltay, Lech Rademacher, Elisabeth Hultgren Hörnquist, Johan Bohr
One to six percent of patients with microscopic colitis are refractory to medical treatment. The effect of faecal microbiota transplantation (FMT) in active collagenous colitis (CC) has, to the best of our knowledge, never been reported before. Here, we report the effect of repeated FMT in a patient with CC. The patient presented with severe symptoms including profuse diarrhea and profound weight loss. Although she responded to budesonide in the beginning, she became gradually refractory to medical treatment, and was therefore treated with FMT...
February 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28246107/comprehensive-meta-analysis-of-key-immune-related-adverse-events-from-ctla-4-and-pd-1-pd-l1-inhibitors-in-cancer-patients
#16
Guillermo De Velasco, Youjin Je, Dominick Bossé, Mark M Awad, Patrick A Ott, Raphael B Moreira, Fabio Schutz, Joaquim Bellmunt, Guru P Sonpavde, F Stephen Hodi, Toni K Choueiri
Immune-related adverse events (irAE) have been described with immune checkpoint inhibitors (ICI), but the incidence and relative risk (RR) of irAEs associated with these drugs remains unclear. We selected five key irAEs from treatments with approved cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed death ligand 1 (PD-L1) inhibitors (ipilimumab, nivolumab, or pembrolizumab, and atezolizumab, respectively) to better characterize their safety profile. We performed a meta-analysis of randomized phase II/III immunotherapy trials, with non-ICI control arms, conducted between 1996 and 2016...
April 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28243458/combination-therapy-with-vedolizumab-and-etanercept-in-a-patient-with-pouchitis-and-spondylarthritis
#17
Johannes Bethge, Silvia Meffert, Mark Ellrichmann, Claudio Conrad, Susanna Nikolaus, Stefan Schreiber
Inflammatory bowel disease is frequently associated with spondylarthritis (SpA). It has been discussed that α4/β7 expressing lymphocytes are involved in the aetiology of SpA. We report a case of a successful combination therapy of vedolizumab (VDZ) and etanercept (ETA) in a patient with ulcerative colitis with pouchitis and SpA. In our case VDZ was effective for pouchitis and ineffective for SpA. The combination with ETA might be a useful treatment strategy to control both diseases and first indications suggest that it is safe...
2017: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/28242647/inhibiting-oxidative-phosphorylation-in-vivo-restrains-th17-effector-responses-and-ameliorates-murine-colitis
#18
Luigi Franchi, Ivan Monteleone, Ling-Yang Hao, Mark A Spahr, Wenpu Zhao, Xikui Liu, Kellie Demock, Aditi Kulkarni, Chuck A Lesch, Brian Sanchez, Laura Carter, Irene Marafini, Xiao Hu, Oksana Mashadova, Min Yuan, John M Asara, Harinder Singh, Costas A Lyssiotis, Giovanni Monteleone, Anthony W Opipari, Gary D Glick
Integration of signaling and metabolic pathways enables and sustains lymphocyte function. Whereas metabolic changes occurring during T cell activation are well characterized, the metabolic demands of differentiated T lymphocytes are largely unexplored. In this study, we defined the bioenergetics of Th17 effector cells generated in vivo. These cells depend on oxidative phosphorylation (OXPHOS) for energy and cytokine production. Mechanistically, the essential role of OXPHOS in Th17 cells results from their limited capacity to increase glycolysis in response to metabolic stresses...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28239462/thrombocytopenia-in-patients-with-melanoma-receiving-immune-checkpoint-inhibitor-therapy
#19
Eileen Shiuan, Kathryn E Beckermann, Alpaslan Ozgun, Ciara Kelly, Meredith McKean, Jennifer McQuade, Mary Ann Thompson, Igor Puzanov, John P Greer, Suthee Rapisuwon, Michael Postow, Michael A Davies, Zeynep Eroglu, Douglas Johnson
BACKGROUND: Immune checkpoint inhibitors, including antibodies against programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are being used with increasing frequency for the treatment of cancer. Immune-related adverse events (irAEs) including colitis, dermatitis, and pneumonitis are well described, but less frequent events are now emerging with larger numbers of patients treated. Herein we describe the incidence and spectrum of thrombocytopenia following immune checkpoint inhibitor therapy and two severe cases of idiopathic thrombocytopenic purpura (ITP)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28223256/role-of-the-leukocyte-response-in-normal-and-immunocompromised-host-after-clostridium-difficile-infection
#20
Edwin Vargas, Senu Apewokin, Rajat Madan
Clostridium difficile is the leading cause of healthcare-associated infections in the United States. Clinically, C. difficile-associated disease can present as asymptomatic colonization, self-limited diarrheal illness or severe colitis (that may result in death). This variability in disease course and outcomes suggests that host factors play an important role as key determinants of disease severity. Currently, there are several scoring indices to estimate severity of C. difficile-associated disease. Leukocytosis and renal failure are considered to be the most important predictors of C...
February 20, 2017: Anaerobe
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