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https://www.readbyqxmd.com/read/28231624/targets-and-mechanisms-in-prevention-of-parkinson-s-disease-through-immunomodulatory-treatments
#1
REVIEW
Marianne von Euler Chelpin, Thomas Vorup-Jensen
Parkinson's Disease (PD) is the second most common neurodegenerative disease in the world, however, there is no cure for it. Current treatments only relieve some of the symptoms, without ceasing the disease, and lose efficacy with prolonged treatment. Considerable evidence shows that persistent inflammatory responses, involving T cell infiltration and glial cell activation, are common characteristics of human patients and play a crucial role in the degeneration of dopaminergic neurons. Therefore, it is important to develop therapeutic strategies that can impede or halt the disease through the modulation of the peripheral immune system by aiming at controlling the existing neuroinflammation...
February 23, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28231426/engineering-of-anti-cd133-tri-specific-molecule-capable-of-inducing-nk-expansion-and-driving-antibody-dependent-cell-mediated-cytotoxicity-adcc
#2
Jörg U Schmohl, Martin Felices, Felix Oh, Alexander J Lenvik, Aaron M Lebeau, Jayanth Panyam, Jeffrey S Miller, Daniel A Vallera
Purpose: The selective elimination of cancer stem cells (CSCs) in tumor patients is a crucial goal because CSCs cause drug refractory relapse. To improve the current conventional bispecific immune-engager platform, a 16133 BiKE, consisting of scFvs binding FcγRIII (CD16) on NK cells and CD133 on carcinoma cells, was first synthesized and a modified IL-15 crosslinker capable of stimulating NK effector cells was introduced. Materials and Methods: DNA shuffling and ligation techniques were used to assemble and synthesize the 1615133 trispecific NK cell engager (TriKE)...
February 20, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28231415/encapsulating-an-immunosuppressant-enhances-tolerance-induction-by-siglec-engaging-tolerogenic-liposomes
#3
Lijuan Pang, Matthew S Macauley, Britni M Arlian, Corwin M Nycholat, James C Paulson
Unwanted antibody responses significantly impact human health, and current options for treating deleterious antibody responses largely rely on broad immunosuppressants that can compromise overall immunity. A desirable alternative is to induce antigen-specific immune tolerance. We have shown that co-presentation of antigen and ligands of B cell Siglecs (sialic acid-binding immunoglobulin-like lectin) on a liposomal nanoparticle induces antigen-specific tolerance. Although Siglec-engaging tolerance-inducing antigenic liposomes (STALs) induce robust B cell tolerance in naïve mice, the full potential of STALs requires long-term tolerance induction and suppression of an ongoing immune response...
February 23, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28231392/from-dendritic-cells-to-b-cells-dysfunctions-during-hiv-1-infection-tfh-at-the-cross-road
#4
REVIEW
Nicolas Ruffin, Lylia Hani, Nabila Seddiki
T follicular helper (Tfh) cells are essential for B cell differentiation and the subsequent antibody responses. Their numbers and functions are altered during human and simian immunodeficiency virus (HIV/SIV) infections. In lymphoid tissues, Tfh cells are present in germinal center, where they are the main source of replicative HIV-1 and represent a major reservoir. Paradoxically, Tfh numbers are increased in chronically infected individuals. Understanding the fate of Tfh cells in the course of HIV-1 infection is essential for the design of efficient strategies toward a protective HIV vaccine or a cure...
February 23, 2017: Immunology
https://www.readbyqxmd.com/read/28230928/reactivation-of-hepatitis-b-in-patients-of-chronic-hepatitis-c-with-hepatitis-b-virus-infection-treated-with-direct-acting-antivirals
#5
Ming-Lun Yeh, Chung-Feng Huang, Meng-Hsuan Hsieh, Yu-Min Ko, Kuan-Yu Chen, Ta-Wei Liu, Yi-Hung Lin, Po-Cheng Liang, Ming-Yen Hsieh, Zu-Yau Lin, Shinn-Cherng Chen, Ching-I Huang, Jee-Fu Huang, Po-Lin Kuo, Chia-Yen Dai, Ming-Lung Yu, Wan-Long Chuang
BACKGROUND AND AIMS: Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy. METHODS: CHC patients receiving pan-oral DAA therapy from Dec. 2013 to Aug. 2016 were evaluated. Fifty-seven patients that had a past HBV infection (negative hepatitis B surface antigen (HBsAg)) and positive hepatitis B core antibody (Anti-HBc)) and 7 patients that had a current HBV infection (positive HBsAg) were enrolled...
February 23, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28230773/programmed-death-ligand-1-pd-l1-tumor-expression-is-associated-with-a-better-prognosis-and-diabetic-disease-in-triple-negative-breast-cancer-patients
#6
Gerardo Botti, Francesca Collina, Giosuè Scognamiglio, Federica Rao, Valentina Peluso, Rossella De Cecio, Michela Piezzo, Gabriella Landi, Michelino De Laurentiis, Monica Cantile, Maurizio Di Bonito
Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230715/a-multireferral-centre-retrospective-cohort-analysis-on-the-experience-in-treatment-of-metastatic-uveal-melanoma-and-utilization-of-sequential-liver-directed-treatment-and-immunotherapy
#7
Malinda Itchins, Paolo A Ascierto, Alexander M Menzies, Meredith Oatley, Serigne Lo, Dariush Douraghi-Zadeh, Timmothy Harrington, Richard Maher, Antonio M Grimaldi, Alexander Guminski
Metastatic uveal melanoma is a rare malignancy with a poor prognosis. To date, systemic therapy has been ineffective; however, there are few data on the benefits of anti-CTLA4 or anti-PD-1 antibodies in sequence with liver-directed therapy. A retrospective cohort analysis was carried out on 37 consecutive patients managed in a tertiary referral centre examining the safety and efficacy of treatment; patterns of care; and impact on survival. The sequential treatment with transarterial chemotherapy (TAC), systemic immunotherapy (IT) and systemic chemotherapy was reviewed...
February 22, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28230657/stabilized-hiv-1-envelope-glycoprotein-trimers-for-vaccine-use
#8
Max Medina-Ramírez, Rogier W Sanders, Quentin J Sattentau
PURPOSE OF REVIEW: To provide an update on the latest developments in the field of HIV-1 antibody-based soluble envelope glycoprotein (Env) trimer design for vaccine use. RECENT FINDINGS: The development of soluble native-like HIV-1 Env trimer immunogens has moved the field of antibody-based vaccine design forward dramatically over the past few years with refinement of various stabilizing approaches. However, despite this progress, significant challenges remain...
February 21, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28230655/lessons-learned-from-human-hiv-vaccine-trials
#9
Justin Pollara, David Easterhoff, Genevieve G Fouda
PURPOSE OF REVIEW: The ability to induce broadly neutralizing antibody (bNAb) responses is likely essential for development of a globally effective HIV vaccine. Unfortunately, human vaccine trials conducted to date have failed to elicit broad plasma neutralization of primary virus isolates. Despite this limitation, in-depth analysis of the vaccine-induced memory B-cell repertoire can provide valuable insights into the presence and function of subdominant B-cell responses, and identify initiation of antibody lineages that may be on a path towards development of neutralization breadth...
February 21, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28230336/the-endothelial-border-to-health-mechanistic-evidence-of-the-hyperglycemic-culprit-of-inflammatory-disease-acceleration
#10
REVIEW
Nina Waerling Hansen, Anker Jon Hansen, Anette Sams
The endothelial cell (EC) layer constitutes a barrier that controls movements of fluid, solutes and cells between blood and tissue. Further, the endothelial layer regulates vascular tone and directs local humoral and cellular inflammatory processes. The strategic position makes it an important player for maintenance of health and for development of a number of diseases. Endothelial dysfunction is known to be an important component of type 2 diabetes, but is also assumed to be involved in many other diseases, for example, rheumatoid arthritis, inflammatory bowel disease, asthma, and cardiovascular diseases...
March 2017: IUBMB Life
https://www.readbyqxmd.com/read/28230306/suppression-of-anti-drug-antibodies-to-infliximab-or-adalimumab-with-the-addition-of-an-immunomodulator-in-patients-with-inflammatory-bowel-disease
#11
A S Strik, G R van den Brink, C Ponsioen, R Mathot, M Löwenberg, G R D'Haens
BACKGROUND: Loss of response to anti-tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD) is often caused by anti-drug antibody formation with neutralisation of drug effect. Addition of an immunomodulator has been suggested to reduce immunogenicity, leading to regained response. AIM: To investigate whether addition of an immunomodulator to anti-TNF monotherapy could lead to anti-drug antibody suppression and regained clinical response in IBD patients...
February 23, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28230186/glycan-independent-binding-and-internalization-of-human-igm-to-fcmr-its-cognate-cellular-receptor
#12
Katy A Lloyd, Jiabin Wang, Britta C Urban, Daniel M Czajkowsky, Richard J Pleass
IgM is the first antibody to be produced in immune responses and plays an important role in the neutralization of bacteria and viruses. Human IgM is heavily glycosylated, featuring five N-linked glycan sites on the μ chain and one on the J-chain. Glycosylation of IgG is known to modulate the effector functions of Fcγ receptors. In contrast, little is known about the effect of glycosylation on IgM binding to the human Fcμ receptor (hFCMR). In this study, we identify the Cμ4 domain of IgM as the target of hFCMR, and show that binding and internalization of IgM by hFCMR is glycan-independent...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229892/safety-and-efficacy-of-opicinumab-in-acute-optic-neuritis-renew-a-randomised-placebo-controlled-phase-2-trial
#13
Diego Cadavid, Laura Balcer, Steven Galetta, Orhan Aktas, Tjalf Ziemssen, Ludo Vanopdenbosch, Jette Frederiksen, Mark Skeen, Glenn J Jaffe, Helmut Butzkueven, Focke Ziemssen, Luca Massacesi, Yi Chai, Lei Xu, Stefanie Freeman
BACKGROUND: The human monoclonal antibody opicinumab (BIIB033, anti-LINGO-1) has shown remyelinating activity in preclinical studies. We therefore assessed the safety and tolerability, and efficacy of opicinumab given soon after a first acute optic neuritis episode. METHODS: This randomised, double-blind, placebo-controlled, phase 2 study (RENEW) was done at 33 sites in Australia, Canada, and Europe in participants (aged 18-55 years) with a first unilateral acute optic neuritis episode within 28 days from study baseline...
March 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28229830/neutrophil-extracellular-traps-formation-in-patients-with-eosinophilic-granulomatosis-with-polyangiitis-association-with-eosinophilic-inflammation
#14
Joanna Natorska, Michał Ząbczyk, Jakub Siudut, Piotr Krawiec, Lucyna Mastalerz, Anetta Undas
OBJECTIVES: Eosinophilic granulomatosis with polyangiitis (EGPA) is associated with an inflammation and the presence of antineutrophil cytoplasmic antibodies (ANCA). Thus, we investigated the impact of ANCAs and eosinophilic inflammation on neutrophil activation and extracellular traps (NETs) formation. METHODS: We recruited 29 patients in the remission of EGPA (17 ANCA-negative and 12 ANCA-positive, including 7 p-ANCA-positive and 5 c-ANCA-positive patients). Healthy donors' neutrophils were stimulated with EGPA patients' serum...
February 9, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28229535/enrichment-and-viability-inhibition-of-circulating-tumor-cells-on-a-dual-acid-responsive-composite-nanofiber-film
#15
Wenqian Wang, Yaya Cheng, Yansheng Li, Hao Zhou, Li-Ping Xu, Yongqiang Wen, Liang Zhao, Xueji Zhang
The formation and metastatic colonization of circulating tumor cells (CTCs) are responsible for the vast majority of cancer-related deaths. Over the last decade, drug delivery system (DDS) has been rapidly developed with nanotechnology arising, however, most of the reported tumor-targeting DDSs were just able to deliver drugs to the solid tumor cells but not CTCs. In here, a novel drug delivery system was constructed with composite nanofiber film to inhibit the viability of circulating tumor cells (CTCs). In this system, gold nanoparticles (Au NPs) were functionalized with doxorubicin (DOX) through an acid-responsive cleavable linker to get the Au-DOX NPs...
February 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28228834/anti-collapsing-response-mediating-protein-5-antibody-positive-paraneoplastic-perioptic-neuritis-without-typical-neurological-symptoms
#16
Nozomi Igarashi, Hiromasa Sawamura, Toshikatsu Kaburaki, Makoto Aihara
A 68-year-old male presented with blurred vision in both eyes. Ophthalmoscopy revealed bilateral prominent disc swelling and vitritis. No systematic neurological symptoms were observed. Magnetic resonance imaging revealed bilateral meningeal enhancement of the optic nerve. Small cell carcinoma was found, and antibodies against collapsing response-mediating protein-5 (CRMP-5) were detected in the serum. Ophthalmological manifestations disappeared during a decrease in tumour size with treatment for the malignancy...
February 2017: Neuro-ophthalmology
https://www.readbyqxmd.com/read/28228737/schizophrenia-associated-with-epileptiform-discharges-without-seizures-successfully-treated-with-levetiracetam
#17
Dominique Endres, Evgeniy Perlov, Bernd Feige, Dirk-Matthias Altenmüller, Nils Venhoff, Ludger Tebartz van Elst
BACKGROUND: Schizophrenia-like disorders can be divided into endogenic or primary, idiopathic, polygenetic forms, and different secondary, organic subgroups [e.g., (para)epileptic, immunological, degenerative]. Epileptic and paraepileptic explanatory approaches have a long tradition due to the high rate of electroencephalography (EEG) alterations in patients with schizophrenia. CASE PRESENTATION: We present the case of a 23-year-old female patient suffering, since the age of 14 years, from a fluctuating paranoid-hallucinatory syndrome with formal thought disorder, fear, delusions of persecution, auditory, visual, and tactile hallucinations, as well as negative and cognitive symptoms...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28228594/the-b-cell-response-to-foot-and-mouth-disease-virus-in-cattle-following-sequential-vaccination-with-multiple-serotypes
#18
Clare F J Grant, B Veronica Carr, Abhay Kotecha, Erwin van den Born, David I Stuart, John A Hammond, Bryan Charleston
Foot-and mouth disease virus is a highly contagious viral disease. Antibodies are pivotal in providing protection against FMDV infection. Serological protection against one FMDV serotype doesn't confer inter-serotypic protection. However, some historical data have shown inter-serotypic protection can be induced following sequential FMDV challenge with multiple FMDV serotypes. In this study we have investigated the kinetics of the FMDV-specific antibody secreting cell response following homologous and heterologous inactivated FMDV vaccination regimes...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228587/prophylactic-herpes-simplex-virus-2-hsv-2-vaccines-adjuvanted-with-stable-emulsion-and-toll-like-receptor-9-agonist-induce-a-robust-hsv-2-specific-cell-mediated-immune-response-protect-against-symptomatic-disease-and-reduce-the-latent-viral-reservoir
#19
Michael T Hensel, Jason D Marshall, Michael R Dorwart, Darren S Heeke, Eileen Rao, Padmaja Tummala, Li Yu, Gary H Cohen, Roselyn J Eisenberg, Derek D Sloan
Several prophylactic vaccines targeting HSV-2 have failed in the clinic to demonstrate a sustained depression in viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies, their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the neutralizing antibody (nAb) targets gD and gB, the novel T cell antigen and tegument protein UL40, and we compared this to a whole-inactivated virus vaccine (FI-HSV-2)...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228559/targeting-influenza-virus-hemagglutinin-to-xcr1-dendritic-cells-in-the-absence-of-receptor-mediated-endocytosis-enhances-protective-antibody-responses
#20
Arnar Gudjonsson, Anna Lysén, Sreekumar Balan, Vibeke Sundvold-Gjerstad, Catharina Arnold-Schrauf, Lisa Richter, Espen S Bækkevold, Marc Dalod, Bjarne Bogen, Even Fossum
Targeting Ags to conventional dendritic cells can enhance Ag-specific immune responses. Although most studies have focused on the induction of T cell responses, the mechanisms by which targeting improves Ab responses are poorly understood. In this study we present data on the use of human XCL1 (hXCL1) and hXCL2 fusion vaccines in a murine model. We show that the human chemokines bound type 1 conventional dendritic cells (cDC1), and that immunization with influenza virus hemagglutinin fused to hXCL1 or hXCL2 induced full protection against influenza challenge...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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