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https://www.readbyqxmd.com/read/28344807/ipilimumab-induced-thrombotic-thrombocytopenic-purpura-ttp
#1
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
#2
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
#3
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...
March 14, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28294127/orai2-modulates-store-operated-calcium-entry-and-t-cell-mediated-immunity
#4
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
#5
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
#6
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...
March 5, 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
#7
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
#8
Guillermo De Velasco, Youjin Je, Dominick Bossé, Mark M Awad, Patrick A Ott, Raphael B Moreira, Fabio A B Schutz, Joaquim Bellmunt, Guru Sonpavde, F Stephen Hodi, Toni K Choueiri
Immune-related adverse events (irAEs) have been described with immune checkpoint inhibitors (ICIs), 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...
February 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28243458/combination-therapy-with-vedolizumab-and-etanercept-in-a-patient-with-pouchitis-and-spondylarthritis
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28215538/over-90-of-cases-of-microscopic-colitis-can-be-diagnosed-by-performing-a-short-colonoscopy
#13
Gilles Macaigne, Pierre Lahmek, Christophe Locher, Jean François Boivin, Bruno Lesgourgues, Mathieu Yver, Laurent Costes, I Abd Alsamad, Joel Cucherousset, Claire Charpignon, Hélène Guyot, Bénédicte Lambaré, Jean-Michel Ghilain, Valérie Calès, Stéphanie de Montigny-Lenhardt, Guy Bellaïche, Alexandre Pariente, Stéphane Nahon
AIMS: To determinate the topographical distribution of key diagnostic histological features of lymphocytic colitis (LC) and collagenous colitis (CC) and to establish what correlations may exist between the histological findings and the causes and severity of MC. PATIENTS AND METHODS: Patients with MC were included in a prospective multicentre French study from September 2010 to October 2012. MC was diagnosed by performing total colonoscopy with multiple biopsies of the rectum and colon collected in separate jars and analyzed separately for each site (descending and sigmoid colon, transverse colon, ascending colon)...
February 16, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28204866/vedolizumab-treatment-for-immune-checkpoint-inhibitor-induced-enterocolitis
#14
Viktoria Bergqvist, Erik Hertervig, Peter Gedeon, Marija Kopljar, Håkan Griph, Sara Kinhult, Ana Carneiro, Jan Marsal
Immune checkpoint inhibitors (ICPI), such as ipilimumab [anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody] and nivolumab or pembrolizumab [anti-programmed cell death protein-1 (PD-1) antibodies], improve survival in several cancer types. Since inhibition of CTLA-4 or PD-1 leads to non-selective activation of the immune system, immune-related adverse events (irAEs) are frequent. Enterocolitis is a common irAE, currently managed with corticosteroids and, if necessary, anti-tumor necrosis factor-α therapy...
February 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28177967/the-neutralizing-and-targeting-properties-of-a-new-set-of-%C3%AE-4%C3%AE-7-specific-antibodies-are-influenced-by-their-isotype
#15
Alexandre Girard, Katija Jelicic, Don Van Ryk, Nicolas Rochereau, Claudia Cicala, James Arthos, Christian Genin, Bernard Verrier, Stephanie Laurant, Diane Razanajaoana-Doll, Pin Jean-Jacques, Stéphane Paul
The homing of lymphocytes to mucosa is mainly controlled by α4β7 integrin, and it is amplified during gut chronic inflammation, as occurs with HIV and/or Inflammatory Bowel Diseases. We designed and applied an improved immunization strategy based on an innovative selection process to isolate new α4β7 lymphocyte-specific mAbs that are able to prevent their migration into inflamed gut tissues and/or to counteract HIV infection in vitro. Firstly, five mAbs (one IgA, one IgM, and four IgGs) were selected based on their capacity to recognize α4 or β7 homodimers and α4β7 heterodimers in transfected human cells...
February 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28172795/p427-neutrophil-to-lymphocyte-ration-in-ulcerative-colitis-predicts-sustained-response-to-infliximab
#16
Y Nishida, S Hosomi, K Watanabe, T Yukawa, K Otani, Y Nagami, F Tanaka, K Taira, N Kamata, M Shiba, H Yamagami, T Tanigawa, T Watanabe, K Tominaga, Y Fujiwara
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28172589/p014-mucosal-lymphocyte-subsets-in-ulcerative-colitis-at-diagnosis-and-during-follow-up
#17
C Smids, C Horjus Talabur Horje, M Groenen, E van Koolwijk, P Wahab, E van Lochem
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28172476/p208-long-term-follow-up-of-lymphocytic-colitis-patients
#18
G Mohamed, P Crotty, D McNamara, N Breslin, B M Ryan
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28164626/expression-of-cd200r1-and-its-ligand-cd200-on-t-helper-lymphocytes-of-pediatric-patients-with-ulcerative-colitis-and-crohn-s-disease
#19
Mohamed F Elshal, Alia M Aldahlawi, Omar I Saadah, J Philip Mccoy
BACKGROUND: CD200 and its receptor CD200R are both type I membrane glycoproteins that modulate the activity of myeloid and lymphoid cells, and their interaction is functionally important in the suppression of effector T-cell responses by regulatory T-cells. We aimed to investigate the extent of expression of CD200 and CD200R1 on CD4+ T-cells in blood of children with ulcerative colitis (UC) and Crohn's disease (CD) and to explore their correlations with effector T cell subsets, regulatory T cells (Treg), and routine clinical and serological markers...
August 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28138755/epithelial-barrier-dysfunction-in-lymphocytic-colitis-through-cytokine-dependent-internalization-of-claudin-5-and-8
#20
Christian Barmeyer, Irene Erko, Karem Awad, Anja Fromm, Christian Bojarski, Svenja Meissner, Christoph Loddenkemper, Martin Kerick, Britta Siegmund, Michael Fromm, Michal R Schweiger, Jörg-Dieter Schulzke
BACKGROUND: Watery diarrhea is the cardinal symptom of lymphocytic colitis (LC). We have previously shown that colonic Na malabsorption is one of the major pathologic alterations of LC and found evidence for an epithelial barrier defect. On these grounds, this study aimed to identify the inherent mechanisms of this epithelial barrier dysfunction and its regulatory features. METHODS: Epithelial resistance (R (epi)) was determined by one-path impedance spectroscopy and (3)H-mannitol fluxes were performed on biopsies from sigmoid colon in miniaturized Ussing chambers...
January 30, 2017: Journal of Gastroenterology
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