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Immunosuppressive therapy

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https://www.readbyqxmd.com/read/28723333/enhanced-prophylaxis-plus-antiretroviral-therapy-for-advanced-hiv-infection-in-africa
#1
James Hakim, Victor Musiime, Alex J Szubert, Jane Mallewa, Abraham Siika, Clara Agutu, Simon Walker, Sarah L Pett, Mutsa Bwakura-Dangarembizi, Abbas Lugemwa, Symon Kaunda, Mercy Karoney, Godfrey Musoro, Sheila Kabahenda, Kusum Nathoo, Kathryn Maitland, Anna Griffiths, Margaret J Thomason, Cissy Kityo, Peter Mugyenyi, Andrew J Prendergast, A Sarah Walker, Diana M Gibb
Background In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. Methods In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter...
July 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28722255/drug-drug-interactions-between-triazole-antifungal-agents-used-to-treat-invasive-aspergillosis-and-immunosuppressants-metabolized-by-cytochrome-p450-3a4
#2
REVIEW
Andreas H Groll, Robert Townsend, Amit Desai, Nkechi Azie, Mark Jones, Marc Engelhardt, Anne-Hortense Schmitt-Hoffman, Robert J Brüggemann
Patients undergoing treatment with immunosuppressant drugs following solid organ or hematopoietic stem cell transplantation are at particular risk for development of serious infections such as invasive aspergillosis. Four triazole antifungal drugs, voriconazole, posaconazole, itraconazole, and isavuconazole, are approved to treat invasive aspergillosis either as first- or second-line therapy. All of these agents are inhibitors of cytochrome P450 3A4, which plays a key role in metabolizing immunosuppressant drugs such as cyclosporine, tacrolimus, and sirolimus...
July 19, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28722017/the-role-of-age-related-t-cell-differentiation-in-patients-with-renal-replacement-therapy
#3
Matthias Schaier, Angele Leick, Lorenz Uhlmann, Florian Kälble, Volker Eckstein, Anthony Ho, Stefan Meuer, Karsten Mahnke, Claudia Sommerer, Martin Zeier, Andrea Steinborn
Dialysis patients have deficiencies regarding the generation of immune responses and show an increased susceptibility for infections. Persisting uremic conditions are made responsible for the increased aging of their immune system. In this study, we analyzed whether age-related differences in the differentiation of both recent-thymic-emigrant-(RTE)-regulatory (Tregs) and RTE-responder T cells (Tresps) into CD31(-)-memory Tregs/Tresps led to differences in the suppressive activity of naïve and memory Tregs on autologous Tresps between healthy volunteers and dialysis patients...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28721208/new-perspectives-on-the-regulation-of-type-ii-inflammation-in-asthma
#4
REVIEW
Mireya Becerra-Díaz, Marsha Wills-Karp, Nicola M Heller
Asthma is a chronic inflammatory disease of the lungs which has been thought to arise as a result of inappropriately directed T helper type-2 (Th2) immune responses of the lungs to otherwise innocuous inhaled antigens. Current asthma therapeutics are directed towards the amelioration of downstream consequences of type-2 immune responses (i.e. β-agonists) or broad-spectrum immunosuppression (i.e. corticosteroids). However, few approaches to date have been focused on the primary prevention of immune deviation...
2017: F1000Research
https://www.readbyqxmd.com/read/28720430/oncogenic-pathways-that-affect-antitumor-immune-response-and-immune-checkpoint-blockade-therapy
#5
REVIEW
Xianda Zhao, Subbaya Subramanian
Mechanistic insights of cancer immunology have led to the development of immune checkpoint blockade therapy (ICBT), which has elicited a remarkable clinical response in some cancer patients. Increasing evidence suggests that activation of oncogenic pathways, such as RAS/RAF/MAPK and PI3K signaling, impairs the antitumor immune response. Such oncogenic signaling, in turn, activates many inhibitory factors, including expression of immune checkpoint genes-allowing active infiltration of immunosuppressive cells into the tumor environment and inducing resistance against T-cell killing...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28719723/de-novo-hhv-8-tumors-induced-by-rituximab-in-autoimmune-or-inflammatory-systemic-diseases
#6
Amandine Perier, Léa Savey, Anne-Geneviève Marcelin, Philippe Serve, David Saadoun, Stéphane Barete
OBJECTIVES: HHV-8, also known as Kaposi's sarcoma (KS) associated herpesvirus is involved in KS and other tumors comprising multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL). Rituximab is currently used for treatment of several autoimmune or inflammatory diseases and humoral organ rejection. De novo HHV-8 induced tumors by rituximab used for autoimmune or inflammatory diseases or humoral organ rejection have not been reported. METHODS: In this retrospective study, we report clinical, virological and pathology of five HIV-negative male patients with HHV-8-induced tumors following rituximab therapy...
July 18, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28719632/viscum-album-neutralizes-tumor-induced-immunosuppression-in-a-human-in-vitro-cell-model
#7
Carmen Steinborn, Amy Marisa Klemd, Ann-Sophie Sanchez-Campillo, Sophie Rieger, Marieke Scheffen, Barbara Sauer, Manuel Garcia-Käufer, Konrad Urech, Marie Follo, Annekathrin Ücker, Gunver Sophia Kienle, Roman Huber, Carsten Gründemann
Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI) on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays...
2017: PloS One
https://www.readbyqxmd.com/read/28719615/a-human-tissue-based-functional-assay-platform-to-evaluate-the-immune-function-impact-of-small-molecule-inhibitors-that-target-the-immune-system
#8
Cristina St Pierre, Jane Guo, John D Shin, Laura W Engstrom, Hyun-Hee Lee, Alan Herbert, Laura Surdi, James Baker, Michael Salmon, Sanjiv Shah, J Michael Ellis, Hani Houshyar, Michael A Crackower, Melanie A Kleinschek, Dallas C Jones, Alexandra Hicks, Dennis M Zaller, Stephen E Alves, Ravisankar A Ramadas
While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28719552/immune-checkpoint-inhibitors-in-organ-transplant-patients
#9
Adam S Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant...
July 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28719391/pediatric-and-congenital-hand-transplantation
#10
Sandra Amaral, L Scott Levin
PURPOSE OF REVIEW: We review the approach and challenges associated with pediatric hand transplantation, including new knowledge gleaned from our recent case of bilateral hand-forearm transplantation in an 8-year old child. RECENT FINDINGS: Bilateral heterologous hand-forearm transplantation was performed in a child with a prior kidney transplant in July 2015. The initial surgery necessitated a large team of experts in microvascular surgery, transplant surgery, orthopedics and plastic surgery as well as pediatric anesthesia...
July 14, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28719256/therapeutic-dilemma-of-refractory-erythema-nodosum-leprosum
#11
Jianyu Zhu, Degang Yang, Chao Shi, Zhichun Jing
AbstractErythema nodosum leprosum (ENL), also known as type II leprosy reaction, is a severe immune-mediated complication of multibacillary leprosy. For ENL, corticosteroids and thalidomide are the mainstays of treatment. Other immunosuppressants, such as clofazimine, cyclosporine, and azathioprine have also been used. Although most patients with ENL respond well to conventional treatments, a small number are refractory to these therapies and have severe morbidity or mortality. We report the case of a 24-year-old man with refractory ENL treated with high-dose corticosteroids for 15 months...
June 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28718428/ifn-signaling-and-icb-resistance-time-is-on-tumor-s-side
#12
Alejandro López-Soto, Segundo Gonzalez, Alicia R Folgueras
Activation of antitumor immunity upon immune checkpoint blockade (ICB) is one of the most promising strategies in cancer therapy. However, ICB resistance is frequently observed in cancer preclinical models and patients. A recent report in Cell reveals that sustained interferon (IFN) signaling confers tumor resistance to ICB by inducing the expression of an immunosuppressive multigenic program.
March 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718424/targeted-therapy-and-immunosuppression-in-the-tumor-microenvironment
#13
REVIEW
Michael J Allegrezza, Jose R Conejo-Garcia
Small-molecule inhibitors offer great promise for targeting pathways that are specifically deregulated in different tumors. However, such 'targeted' therapies also elicit poorly understood effects on protective antitumor immunity. Given the emerging relevance of immunotherapies that boost pre-existing T cell responses, understanding how different immune cells are affected by small-molecule inhibitors could lead to more-effective interventions, alone or combined with immunotherapy. This review discusses the growing array of activities elicited by multiple 'targeted' inhibitors on antitumor immunity, underscoring the complex effects resulting from diverse activities on different immune cell types in vivo, and the need to conduct mechanistic research that identifies drugs performing well not only in immunocompromised mice but also in the presence of spontaneous or therapeutic antitumor immunity...
January 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718404/emerging-role-of-the-unfolded-protein-response-in-tumor-immunosurveillance
#14
REVIEW
Hélène Vanacker, Jessica Vetters, Lyvia Moudombi, Christophe Caux, Sophie Janssens, Marie-Cécile Michallet
Disruption of endoplasmic reticulum (ER) homeostasis results in ER stress and activation of the unfolded protein response (UPR). This response alleviates cell stress, and is activated in both tumor cells and tumor infiltrating immune cells. The UPR plays a dual function in cancer biology, acting as a barrier to tumorigenesis at the premalignant stage, while fostering cancer maintenance in established tumors. In infiltrating immune cells, the UPR has been involved in both immunosurveillance and immunosuppressive functions...
July 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28717938/rituximab-in-steroid-sensitive-nephrotic-syndrome-lessons-from-clinical-trials
#15
REVIEW
Kazumoto Iijima, Mayumi Sako, Koichi Kamei, Kandai Nozu
Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. A total of 80-90% of patients with childhood idiopathic nephrotic syndrome achieve remission with steroid therapy [steroid-sensitive nephrotic syndrome (SSNS)]. However, approximately 50% of children with SSNS develop frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Children with FRNS or SDNS are usually treated with immunosuppressive agents, but 10-20% of children receiving immunosuppressive agents still show frequent relapses or steroid dependence during or after treatment, defined as complicated FRNS or SDNS...
July 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28717935/rabbit-anti-human-thymocyte-immunoglobulin-for-the-rescue-treatment-of-chronic-antibody-mediated-rejection-after-pediatric-kidney-transplantation
#16
Yasemen Cihan, Nele Kanzelmeyer, Jens Drube, Martin Kreuzer, Christian Lerch, Imke Hennies, Kerstin Froede, Murielle Verboom, Thurid Ahlenstiel-Grunow, Lars Pape
BACKGROUND: Chronic antibody-mediated rejection (cAMR) is the leading cause of late kidney graft loss, but current therapies are often ineffective. Rabbit anti-human thymocyte immunoglobulin (rATG) may be helpful, but its use is virtually undocumented. METHODS: Data were analyzed retrospectively from nine pediatric kidney transplant patients with cAMR were treated with rATG (1.5 mg/kg × 5 days) at our center after non-response to pulsed prednisolone, intravenous immunoglobulin, rituximab, and increased immunosuppressive intensity (including switching to belatacept in some cases), with or without bortezomib...
July 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28717088/long-term-effects-of-intravenous-cyclophosphamide-in-combination-with-mesna-provided-intravenously-and-via-bladder-perfusion-in-a-patient-with-severe-multifocal-motor-neuropathy
#17
Eri Iwasawa, Takuya Ohkubo, Tadashi Kanouchi, Takashi Kanda, Hidehiro Mizusawa, Takanori Yokota
A 25-year-old woman presenting with progressive muscle weakness in the distal extremities in the absence of sensory involvement for 2 years was diagnosed with multifocal motor neuropathy (MMN). Her disease was difficult to manage with various immunosuppressants, and the muscle weakness eventually progressed to involve the respiratory muscles, necessitating mechanical ventilation. Intravenous cyclophosphamide (CY) dramatically improved her symptoms, and she has since maintained her ambulatory status for 18 years with intermittent CY therapy...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28717075/clinical-characteristics-of-bacteremia-caused-by-extended-spectrum-beta-lactamase-producing-escherichia-coli-at-a-tertiary-hospital
#18
Hiroki Namikawa, Koichi Yamada, Hiroki Fujimoto, Ken-Ichi Oinuma, Yoshihiro Tochino, Yasuhiko Takemoto, Yukihiro Kaneko, Taichi Shuto, Hiroshi Kakeya
Objective In recent years, infection caused by extended-spectrum beta-lactamase (ESBL)-producing organisms has become an important issue. However, comparative studies of the bacteremia caused by ESBL Enterobacteriaceae and non-ESBL Enterobacteriaceae are extremely rare in Japan. This study aimed to assess the risk factors and prognosis of patients with bacteremia due to ESBL Escherichia coli (E. coli). Methods The medical records of 31 patients with ESBL E. coli bacteremia and 98 patients with non-ESBL E. coli bacteremia who had been admitted to Osaka City University Hospital between January 2011 and June 2015 were retrospectively reviewed...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28716871/igg4-related-disease-long-term-natural-history-and-management-of-a-relapsing-multisystem-disease-entity
#19
Sreelakshmi Kotha, Giovanni Tritto, Terry Wong, Philip Berry
Although awareness of IgG4-related disease has grown over the past decade, with earlier diagnosis and treatment, understanding of its natural history over the long term and the optimal management remains unclear. We report the case of a 48-year-old man who presented with a pancreatic pseudotumour causing bile duct obstruction with coexisting autoimmune hepatitis and multisystem involvement. His symptoms settled on steroids and maintenance with azathioprine was commenced, however periodic relapses occurred involving multiple organs...
July 16, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28716862/gene-therapy-for-wiskott-aldrich-syndrome-in-a-severely-affected-adult
#20
Emma C Morris, Thomas Fox, Ronjon Chakraverty, Rita Tendeiro, Katie Snell, Christine Rivat, Sarah Grace, Kimberly Gilmour, Sarita Workman, Karen Buckland, Katie Butler, Ronnie Chee, Alan D Salama, Hazem Ibrahim, Havinder Hara, Cecile Duret, Fulvio Mavilio, Frances Male, Frederick D Bushman, Anne Galy, Siobhan O Burns, H Bobby Gaspar, Adrian J Thrasher
Until recently hematopoietic stem cell transplantation was the only curative option for Wiskott-Aldrich syndrome (WAS). The first attempts at gene therapy for WAS using a ϒ-retroviral vector improved immunological parameters substantially but were complicated by acute leukemia as a result of insertional mutagenesis in a high proportion of patients. More recently treatment of children with a state-of-the-art self-inactivating lentiviral vector (LV-w1.6 WASp) has resulted in significant clinical benefit without inducing selection of clones harbouring integrations near oncogenes...
July 17, 2017: Blood
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