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https://www.readbyqxmd.com/read/28531305/impact-of-age-and-antibody-type-on-progression-from-single-to-multiple-autoantibodies-in-type-1-diabetes-relatives
#1
Emanuele Bosi, David C Boulware, Dorothy J Becker, Jane H Buckner, Susan Geyer, Peter A Gottlieb, Courtney Henderson, Amanda Kinderman, Jay M Sosenko, Andrea K Steck, Polly J Bingley
Context: Islet autoantibodies are markers of type 1 diabetes and an increase in number of autoantibodies detected during the preclinical phase is predictive of progression to overt disease. Objective: To refine the impact of age in relation to islet antibody type on the progression from single to multiple autoantibodies in relatives of people with type 1 diabetes. Research design and methods: We examined 994 relatives with normal glucose tolerance and positive for a single autoantibody, followed prospectively in the TrialNet Pathway to Prevention...
May 22, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28529646/peptide-vaccination-in-the-presence-of-adjuvants-in-patients-after-hematopoietic-stem-cell-transplantation-with-cd4-t-cell-reconstitution-elicits-consistent-cd8-t-cell-responses
#2
Michael Schmitt, Anita Schmitt, Markus Wiesneth, Angela Hückelhoven, Zeguang Wu, Jürgen Kuball, Lei Wang, Peter Schauwecker, Susanne Hofmann, Marlies Götz, Birgit Michels, Birgit Maccari, Patrick Wuchter, Volker Eckstein, Thomas Mertens, Paul Schnitzler, Hartmut Döhner, Anthony D Ho, Donald W Bunjes, Peter Dreger, Hubert Schrezenmeier, Jochen Greiner
Rationale: Patients receiving an allogeneic stem cell graft from cytomegalovirus (CMV) seronegative donors are particularly prone to CMV reactivation with a high risk of disease and mortality. Therefore we developed and manufactured a novel vaccine and initiated a clinical phase I trial with a CMV phosphoprotein 65 (CMVpp65)-derived peptide. Methods: Ten patients after allogeneic stem cell transplantation received four vaccinations at a biweekly interval. All patients were monitored for CMVpp65 antigenemia...
2017: Theranostics
https://www.readbyqxmd.com/read/28529635/synthesis-of-5-18-f-fluoro-%C3%AE-methyl-tryptophan-new-trp-based-pet-agents
#3
Benjamin C Giglio, Haiyang Fei, Mengzhe Wang, Hui Wang, Liu He, Huijuan Feng, Zhanhong Wu, Hongjian Lu, Zibo Li
Indoleamine 2,3-dioxygenase (IDO1) plays a special role in the biology of various cancer types, because it breaks down the essential amino acid tryptophan for immune cell activation. Upregulation of IDO1 significantly correlates with the number of various T cell types in tumor tissues in melanoma and other cancers, suggesting that IDO expression is linked with effective and ineffective ('exhausted') immune response in cancer. Based on the reported IDO inhibitors (α-Methylated and indole-N-methylated tryptophan (Trp)), here we report the synthesis of potential IDO1 imaging agents through direct introduction of (18)F into the tryptophan aromatic ring...
2017: Theranostics
https://www.readbyqxmd.com/read/28529560/ruanjian-sanjie-decoction-exhibits-antitumor-activity-by-inducing-cell-apoptosis-in-breast-cancer
#4
Xiumei Zhao, Jing Zhao, Renjie Hu, Qiang Yao, Guixian Zhang, Hongsheng Shen, Ernesto Yagüe, Yunhui Hu
Traditional Chinese medicine, based on theories developed and practiced for >2,000 years, is one of the most common complementary and alternative types of medicine currently used in the treatment of patients with breast cancer. Ruanjian Sanjie (RJSJ) decoction, is composed of four herbs, including Ban xia (Pinellia ternata), Xia ku cao (Prunella vulgaris), Shan ci gu (Cremastra appendiculata) and Hai zao (Sargassum pallidum), and has traditionally been used for softening hard lumps and resolving hard tissue masses...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529551/history-and-current-state-of-immunotherapy-in-glioma-and-brain-metastasis
#5
REVIEW
Tresa McGranahan, Gordon Li, Seema Nagpal
Malignant brain tumors such as glioblastoma (GBM) and brain metastasis have poor prognosis despite conventional therapies. Successful use of vaccines and checkpoint inhibitors in systemic malignancy has increased the hope that immune therapies could improve survival in patients with brain tumors. Manipulating the immune system to fight malignancy has a long history of both modest breakthroughs and pitfalls that should be considered when applying the current immunotherapy approaches to patients with brain tumors...
May 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28529509/a-novel-esat-6-secretion-system-secreted-protein-esxx-of-community-associated-staphylococcus-aureus-lineage-st398-contributes-to-immune-evasion-and-virulence
#6
Yingxin Dai, Yanan Wang, Qian Liu, Qianqian Gao, Huiying Lu, Hongwei Meng, Juanxiu Qin, Mo Hu, Min Li
The ESAT-6 secretion system (ESS) has been reported to contribute to the virulence and pathogenicity of several Staphylococcus aureus strains such as USA300 and Newman. However, the role of the ESS in community-associated S. aureus (CA-SA) lineage ST398 in China is not well understood. By comparing the ess locus of ST398 with the published S. aureus sequence in the NCBI database, we found one gene in the ess locus encoding a novel WXG superfamily protein that is highly conserved only in ST398. LC-MS/MS and Western blot analysis revealed that this protein is a novel secreted protein controlled by the ST398 ESS, and we named the protein EsxX...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28529326/persistent-bacterial-infections-and-persister-cells
#7
REVIEW
Robert A Fisher, Bridget Gollan, Sophie Helaine
Many bacteria can infect and persist inside their hosts for long periods of time. This can be due to immunosuppression of the host, immune evasion by the pathogen and/or ineffective killing by antibiotics. Bacteria can survive antibiotic treatment if they are resistant or tolerant to a drug. Persisters are a subpopulation of transiently antibiotic-tolerant bacterial cells that are often slow-growing or growth-arrested, and are able to resume growth after a lethal stress. The formation of persister cells establishes phenotypic heterogeneity within a bacterial population and has been hypothesized to be important for increasing the chances of successfully adapting to environmental change...
May 22, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28529307/genetic-deletion-of-sost-or-pharmacological-inhibition-of-sclerostin-prevent-multiple-myeloma-induced-bone-disease-without-affecting-tumor-growth
#8
J Delgado-Calle, J Anderson, M D Cregor, K W Condon, S A Kuhstoss, L I Plotkin, T Bellido, G D Roodman
Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl) levels, an osteocyte-derived inhibitor of Wnt/β-catenin signaling, are elevated in MM patient sera and are increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28528762/safety-and-immunogenicity-of-a-prototype-anti-chlamydia-pecorum-recombinant-protein-vaccine-in-lambs-and-pregnant-ewes
#9
Marion Desclozeaux, Martina Jelocnik, Katrina Whitting, Siamak Saifzadeh, Sankhya Bommana, Andrew Potter, Volker Gerdts, Peter Timms, Adam Polkinghorne
Arthritis and kerato-conjunctivitis caused by Chlamydia pecorum in lambs are difficult to diagnose and treat. We tested the ability of a prototype C. pecorum vaccine (SC-vaccine), comprised of C. pecorum major outer membrane protein (MOMP-G) and polymorphic membrane protein G (PmpG), to trigger a Chlamydia-specific humoral and cell-mediated immune response in lambs and pregnant ewes. Vaccinations with the SC-vaccine (one and two injections) were very well tolerated by all ewes and lambs. Although the overall immune responses of ewes to SC-vaccination was poor, their lambs showed stronger antigen-specific immune response than lambs from control vaccine ewes...
May 18, 2017: Vaccine
https://www.readbyqxmd.com/read/28528521/myeloid-populations-in-systemic-autoimmune-diseases
#10
REVIEW
María Morell, Nieves Varela, Concepción Marañón
Systemic autoimmune diseases (SADs) encompass a wide spectrum of clinical signs as a reflection of their complex physiopathology. A variety of mechanisms related with the innate immune system are in the origin of the loss of self-tolerance in these diseases, and for most of them, the myeloid leukocytes are key actors. Monocytes, macrophages, dendritic cells, and neutrophils are first-line immune effectors located in the interface between innate and adaptive immunity. They are crucial in the organization of the local and systemic responses to damage-associated molecular patterns (DAMPs) and determine the intensity, orientation, and duration of the local immune response through the expression of chemokines, costimulatory or protolerogenic factors...
May 20, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28527887/mst1-deficiency-promotes-b-cell-responses-by-cd4-t-cell-derived-il-4-resulting-in-hypergammaglobulinemia
#11
Eunchong Park, Myun Soo Kim, Ju Han Song, Kyung Min Cho, Kyung-Hye Roh, Rana Lee, Tae Sung Kim
MST1 deficiency causes T and B cell lymphopenia, resulting in combined immunodeficiency. However, MST1-deficient patients also exhibit autoimmune-like symptoms such as hypergammaglobulinemia and autoantibody production. Recent studies have shown that the autoimmune responses observed in MST1-deficient patients were most likely attributable to defective regulatory T (Treg) cells instead of intrinsic signals in MST1-lacking B cells. Nevertheless, it is not determined how MST1 deficiency in T cells breaks B cell tolerance and causes systemic autoimmune-like phenotypes...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526855/gut-homeostasis-and-regulatory-t-cell-induction-depend-on-molecular-chaperone-gp96-in-cd11c-cells
#12
Yunpeng Hua, Yi Yang, Shaoli Sun, Stephen Iwanowycz, Caroline Westwater, Boris Reizis, Zihai Li, Bei Liu
The intestinal immunity and tolerance are orchestrated by both the innate and the adaptive immune system. Intestinal professional antigen presenting cells (pAPCs) recognize and respond to the gut microbiota through multiple pattern-recognition receptors, including TLRs and NLRs. How gut pAPCs maintain mucosal homeostasis remains incompletely understood. Heat shock protein gp96, also known as grp94, is an essential immune chaperone for TLRs. However, the role of gp96 in regulating CD11c(+) APCs in the gut immunity and tolerance is unknown...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#13
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28526137/cellular-and-molecular-mechanisms-of-autoimmunity-and-lupus-nephritis
#14
S K Devarapu, G Lorenz, O P Kulkarni, H-J Anders, S R Mulay
Autoimmunity involves immune responses directed against self, which are a result of defective self/foreign distinction of the immune system, leading to proliferation of self-reactive lymphocytes, and is characterized by systemic, as well as tissue-specific, inflammation. Numerous mechanisms operate to ensure the immune tolerance to self-antigens. However, monogenetic defects or genetic variants that weaken immune tolerance render susceptibility to the loss of immune tolerance, which is further triggered by environmental factors...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28523588/advances-in-the-development-of-janus-kinase-inhibitors-in-inflammatory-bowel-disease-future-prospects
#15
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/28522352/immune-plasma-for-the-treatment-of-severe-influenza-an-open-label-multicentre-phase-2-randomised-study
#16
John H Beigel, Pablo Tebas, Marie-Carmelle Elie-Turenne, Ednan Bajwa, Todd E Bell, Charles B Cairns, Shmuel Shoham, Jaime G Deville, Eric Feucht, Judith Feinberg, Thomas Luke, Kanakatte Raviprakash, Janine Danko, Dorothy O'Neil, Julia A Metcalf, Karen King, Timothy H Burgess, Evgenia Aga, H Clifford Lane, Michael D Hughes, Richard T Davey
BACKGROUND: Influenza causes substantial morbidity and mortality despite available treatments. Anecdotal reports suggest that plasma with high antibody titres to influenza might be of benefit in the treatment of severe influenza. METHODS: In this randomised, open-label, multicentre, phase 2 trial, 29 academic medical centres in the USA assessed the safety and efficacy of anti-influenza plasma with haemagglutination inhibition antibody titres of 1:80 or more to the infecting strain...
May 15, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28522011/vaccination-with-a-live-attenuated-acinetobacter-baumannii-deficient-in-thioredoxin-provides-protection-against-systemic-acinetobacter-infection
#17
Sarah Ainsworth, Patrick M Ketter, Jieh-Juen Yu, Rose C Grimm, Holly C May, Andrew P Cap, James P Chambers, M Neal Guentzel, Bernard P Arulanandam
Multi-drug resistant Acinetobacter baumannii (MDR-Ab), an opportunistic pathogen associated with nosocomial and combat related infections, has a high mortality due to its virulence and limited treatment options. Deletion of the thioredoxin gene (TrxA) from a clinical isolate of MDR-Ab resulted in a 100-fold increase in 50% lethal dose (LD50) in a systemic challenge murine model. Thus, we investigated the potential use of this attenuated strain as a live vaccine against MDR-Ab. Mice were vaccinated by subcutaneous (s...
May 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28521905/harnessing-the-properties-of-dendritic-cells-in-the-pursuit-of-immunological-tolerance
#18
REVIEW
Christopher Horton, Kumaran Shanmugarajah, Paul J Fairchild
The acquisition of self-perpetuating, immunological tolerance specific for graft alloantigens has long been described as the "holy grail" of clinical transplantation. By removing the need for life-long immunosuppression following engraftment, the adverse consequences of immunosuppressive regimens, including chronic infections and malignancy, may be avoided. Furthermore, autoimmune diseases and allergy are, by definition, driven by aberrant immunological responses to ordinarily innocuous antigens. The re-establishment of permanent tolerance towards instigating antigens may, therefore, provide a cure to these common diseases...
April 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28521640/antibody-mediated-immunotherapy-against-chronic-hepatitis-b-virus-infection
#19
Ying Gao, Tian-Ying Zhang, Quan Yuan, Ning-Shao Xia
The currently available drugs to treat hepatitis B virus (HBV) infection include interferons and nucleos(t)ide analogues, which can only induce disease remission and are inefficient for the functional cure of patients with chronic HBV infection (CHB). Since high titers of circulating hepatitis B surface antigen (HBsAg) may be essential to exhaust the host anti-HBV immune response and they cannot be significantly reduced by current drugs, new antiviral strategies aiming to suppress serum hepatitis B surface antigen (HBsAg) could help restore virus-specific immune responses and promote the eradication of the virus...
May 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28521429/b-cells-inhibit-the-antitumor-immunity-against-an-established-murine-fibrosarcoma
#20
Andrea Maglioco, Damián G Machuca, María Noel Badano, Paula Nannini, Gabriela V Camerano, Héctor Costa, Roberto Meiss, Raúl A Ruggiero, Mirta Giordano, Graciela I Dran
Despite the classic role of B cells in favoring the immune response, an inhibitory action of B lymphocytes in tumor immunity has emerged in certain studies. In methylcolanthrene-induced murine fibrosarcoma (MCC), the loss of immunogenicity and the establishment of tolerance are paralleled by systemic immune suppression and the appearance of B(+)IL-10(+) cells in tumor-draining lymph nodes. The present study aimed to assess the role of the B(+)IL-10(+) cell population in the immune evasion and tolerance induced by MCC through the depletion of B cells in mice at various times of tumor progression: Prior to or subsequent to tumor implantation...
May 2017: Oncology Letters
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