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Immunological tolerance

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https://www.readbyqxmd.com/read/29155233/autologous-hematopoietic-stem-cell-transplantation-in-systemic-sclerosis-a-reset-to-tolerance
#1
REVIEW
Femke C C van Rhijn-Brouwer, Julia Spierings, Jacob M van Laar
Autologous hematopoietic stem cell transplantation (ASCT) is an effective therapy for refractory autoimmune disease, in particular diffuse cutaneous systemic sclerosis (dcSSc). ASCT is the only treatment that can induce long term remission in dcSSc. However, the mechanism of action of ASCT has not yet been fully elucidated. The current hypothesis is that ASCT induces a long term 'reset' of the immune system, but there is no clear definition yet of such an immunological 'reset to tolerance', nor has it been established how to distinguish a 'reset' from long term immunosuppression...
November 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/29155220/complement-components-as-promoters-of-immunological-tolerance-in-dendritic-cells
#2
REVIEW
Ana Luque, Inmaculada Serrano, Josep M Aran
Complement and dendritic cells (DCs) share many functional features that drive the outcome of immune-inflammatory processes. Both have a sentinel function, acting as danger sensors specialized for a rapid, comprehensive and selective action against potential threats without damaging the healthy host cells. But while complement has been considered as a "master alarm" system poised for direct pathogen killing, DCs are regarded as "master regulators" or orchestrators of a vast range of effector immune cells for an effective immune response against threatening insults...
November 16, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29154959/early-life-innate-immune-signatures-of-persistent-food-allergy
#3
Melanie R Neeland, Jennifer J Koplin, Thanh D Dang, Shyamali C Dharmage, Mimi L Tang, Susan L Prescott, Richard Saffery, David J Martino, Katrina J Allen
BACKGROUND: Food allergy naturally resolves in a proportion of food allergic children without intervention, however the underlying mechanisms governing the persistence or resolution of food allergy in childhood are not understood. OBJECTIVES: This study aimed to define the innate immune profiles associated with egg allergy at one year of age, determine the phenotypic changes that occur with the development of natural tolerance in childhood and explore the relationship between early life innate immune function and serum vitamin D...
November 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29154465/the-role-of-immunological-testing-and-intervention-in-reproductive-medicine-a-fertile-collaboration
#4
REVIEW
Syed B Ali, Yogesh Jeelall, Craig E Pennell, Roger Hart, Andrew McLean-Tooke, Michaela Lucas
Advances in reproductive medicine have significantly increased the success of fertility treatments. Nevertheless, some women experience recurrent implantation failure (RIF) after in-vitro fertilization (IVF) or recurrent pregnancy loss (RPL). Imbalances in the immune system and failure to achieve immune tolerance to the foetus have been implicated as potentially modifiable causes of idiopathic RIF and RPL. As such, women are increasingly being treated with immunomodulatory agents in an attempt to achieve a successful pregnancy...
November 20, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29154073/a-new-topical-treatment-of-atopic-dermatitis-in-pediatric-patients-based-on-ficus-carica-l-fig-a-randomized-placebo-controlled-clinical-trial
#5
Shirin Abbasi, Mohammad Kamalinejad, Delara Babaie, SeyedMohammad Shams, Zahra Sadr, Mehdi Gheysari, Vahid Reza Askari, Hassan Rakhshandeh
BACKGROUND: Atopic dermatitis (AD) is a common, chronic, relapsing and inflammatory skin disease characterized by pruritus and xerosis (dry skin). Its prevalence is on the increase worldwide, particularly in children. As the pathogenesis of AD involves a complex interaction of genetic, environmental and immunological factors, its definitive treatment is difficult. OBJECTIVE: This clinical trial was designed as equivalence study to investigate the effect of aqueous extract of edible dried fig fruit on the severity of AD as measured with scoring atopic dermatitis (SCORAD), in comparison with Hydrocortisone 1...
December 2017: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/29150086/the-ex-vivo-toll-like-receptor-7-tolerance-induction-in-donor-lymphocytes-prevents-murine-acute-graft-versus-host-disease
#6
Nikolaos Zogas, Garyfalia Karponi, Fotios Iordanidis, Stylianos Malasidis, Vasilios Paraskevas, Anastasia Papadopoulou, Zaharias George Scouras, Achilles Anagnostopoulos, Evangelia Yannaki
BACKGROUND AIMS: Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation, mediated by alloreactive donor T cells. Toll-like receptors (TLRs), a family of conserved pattern-recognition receptors (PRRs), represent key players in donors' T-cell activation during aGVHD; however, a regulatory, tolerogenic role for certain TLRs has been recognized in a different context. We investigated whether the ex vivo-induced TLR-2,-4,-7 tolerance in donor cells could prevent alloreactivity in a mismatched transplantation model...
November 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29147605/egfr-mutation-correlates-with-uninflamed-phenotype-and-weak-immunogenicity-causing-impaired-response-to-pd-1-blockade-in-non-small-cell-lung-cancer
#7
Zhong-Yi Dong, Jia-Tao Zhang, Si-Yang Liu, Jian Su, Chao Zhang, Zhi Xie, Qing Zhou, Hai-Yan Tu, Chong-Rui Xu, Li-Xu Yan, Yu-Fa Li, Wen-Zhao Zhong, Yi-Long Wu
Patients with EGFR mutations showed unfavorable response to programmed cell death-1 (PD-1) blockade immunotherapy in non-small cell lung cancer (NSCLC). Yet the underlying association between EGFR mutation and immune resistance remains largely unclear. We performed an integrated analysis of PD-ligand 1(PD-L1)/CD8 expression and mutation profile based on the repository database and resected early-stage NSCLC in Guangdong Lung Cancer Institute (GLCI). Meanwhile, 2 pool-analyses were set to clarify the correlation between EGFR mutation and PD-L1 expression, and the association of EGFR status with response to anti-PD-1/L1 therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146246/nanoparticle-formulation-improves-doxorubicin-efficacy-by-enhancing-host-antitumor-immunity
#8
Eric M Mastria, Leon Y Cai, Matthew J Kan, Xinghai Li, Jeffrey L Schaal, Steven Fiering, Michael D Gunn, Mark W Dewhirst, Smita K Nair, Ashutosh Chilkoti
Strategies that enhance the host antitumor immune response promise to revolutionize cancer therapy. Optimally mobilizing the immune system will likely require a multi-pronged approach to overcome the resistance developed by tumors to therapy. Recently, it has become recognized that doxorubicin can contribute to re-establishing host antitumor immunity through the generation of immunogenic cell death. However, the potential for delivery strategies to further enhance the immunological effects of doxorubicin has not been adequately examined...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29146214/-treatments-of-steroid-dependent-nephrotic-syndrome-in-children
#9
A Couderc, E Bérard, V Guigonis, I Vrillon, J Hogan, V Audard, V Baudouin, C Dossier, O Boyer
Primary nephrotic syndrome (NS) is the most common glomerular disease in children. It is characterized by massive proteinuria and hypoalbuminemia. It typically has a sudden onset and more than 70% of patients will experience at least one relapse. An immunological origin has long been postulated, although the precise molecular mechanisms underlying the disease remain debated. Steroids are the first-line therapy with cumulative dose and duration of initial treatment varying among countries. Steroid-sparing agents may be indicated in case of steroid-dependency or frequent relapses...
November 13, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/29144049/characterization-of-children-with-recurrent-eczema-herpeticum-and-response-to-treatment-with-interferon-gamma
#10
Kavita Darji, Stephanie Frisch, Eric Adjei Boakye, Elaine Siegfried
BACKGROUND/OBJECTIVES: Interferon gamma (IFN-γ) has been used treat severe atopic dermatitis, with equivocal results. Recurrent eczema herpeticum is an underappreciated, therapeutically challenging complication of severe atopic dermatitis. Defects in IFN-γ and other cytokine pathways have been identified in individuals with confirmed eczema herpeticum. This suggests possible benefit from IFN-γ treatment for confirmed eczema herpeticum. The objective of the current study was to evaluate immunologic and microbial parameters and response to IFN-γ treatment in children with confirmed eczema herpeticum...
November 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/29141886/pd-l1-genetic-overexpression-or-pharmacological-restoration-in-hematopoietic-stem-and-progenitor-cells-reverses-autoimmune-diabetes
#11
Moufida Ben Nasr, Sara Tezza, Francesca D'Addio, Chiara Mameli, Vera Usuelli, Anna Maestroni, Domenico Corradi, Silvana Belletti, Luca Albarello, Gabriella Becchi, Gian Paolo Fadini, Christian Schuetz, James Markmann, Clive Wasserfall, Leonard Zon, Gian Vincenzo Zuccotti, Paolo Fiorina
Immunologically based clinical trials performed thus far have failed to cure type 1 diabetes (T1D), in part because these approaches were nonspecific. Because the disease is driven by autoreactive CD4 T cells, which destroy β cells, transplantation of hematopoietic stem and progenitor cells (HSPCs) has been recently offered as a therapy for T1D. Our transcriptomic profiling of HSPCs revealed that these cells are deficient in programmed death ligand 1 (PD-L1), an important immune checkpoint, in the T1D nonobese diabetic (NOD) mouse model...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29141313/-tocilizumab-for-refractory-systemic-juvenile-idiopathic-arthritis
#12
J M Lai, F Q Wu, Z X Zhou, M Kang, X L Huang, G X Su, S N Li, J Zhu, X N Wang
Objective: To evaluate the efficacy and side effects of tocilizumab for the treatment of systemic juvenile idiopathic arthritis. Method: In this prospective self case-control study, the children diagnosed with refractory systemic juvenile idiopathic arthritis admitted to Department of Rheumatism and Immunology of Children's Hospital Affiliated to Capital Institute of Pediatrics from December 2013 to June 2016 were enrolled and information before and after treatment of tocilizumab was analyzed. The tocilizumab was introvenously guttae in a dose of 8-12 mg/kg every 2 weeks...
November 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29140828/biomimetic-nanoparticles-for-transplantation-tolerance
#13
Silvia Minardi, Sahil Shah, Xunrong Luo
PURPOSE OF REVIEW: The current review aims to provide a current landscape and future trends of biomimetic nanoparticles which have the potential to revolutionize the field of transplantation in the next decade. RECENT FINDINGS: Currently, the inability to safely induce robust donor-specific immunological tolerance makes it difficult to achieve immunosuppression-free graft survival. Despite progresses in the development of nanotherapeutics for antigen-specific immunomodulation in autoimmune diseases and in cancer treatments, few have been proposed and tested in transplantation with success...
November 14, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29136037/safety-pharmacokinetics-and-immunological-activities-of-multiple-intravenous-or-subcutaneous-doses-of-an-anti-hiv-monoclonal-antibody-vrc01-administered-to-hiv-uninfected-adults-results-of-a-phase-1-randomized-trial
#14
Kenneth H Mayer, Kelly E Seaton, Yunda Huang, Nicole Grunenberg, Abby Isaacs, Mary Allen, Julie E Ledgerwood, Ian Frank, Magdalena E Sobieszczyk, Lindsey R Baden, Benigno Rodriguez, Hong Van Tieu, Georgia D Tomaras, Aaron Deal, Derrick Goodman, Robert T Bailer, Guido Ferrari, Ryan Jensen, John Hural, Barney S Graham, John R Mascola, Lawrence Corey, David C Montefiori
BACKGROUND: VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. METHODS AND FINDINGS: HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29135830/tissue-resident-lymphocytes-in-solid-organ-transplantation-innocent-passengers-or-the-key-to-organ-transplant-survival
#15
Amy C Prosser, Axel Kallies, Michaela Lucas
Short-term outcomes of solid organ transplantation have improved dramatically over the past several decades; however, long-term survival has remained static over the same time period, and chronic rejection remains a major cause of graft failure. The importance of donor, or 'passenger', lymphocytes to the induction of tolerance to allografts was recognized in the 1990s; however, their precise contribution to graft acceptance or rejection has not been elucidated. Recently, specialized populations of tissue-resident lymphocytes in nonlymphoid organs have been described...
November 14, 2017: Transplantation
https://www.readbyqxmd.com/read/29131413/the-effect-of-epitope-based-ligation-of-icam-1-on-survival-and-retransplantation-of-pig-islets-in-nonhuman-primates
#16
Jae-Il Lee, Jiyeon Kim, Yun-Jung Choi, Hi-Jung Park, Hye-Jin Park, Hae Joo Wi, Sunok Yoon, Jun-Seop Shin, Jin Kyun Park, Kyeong Cheon Jung, Eun Bong Lee, Hee Jung Kang, Eung Soo Hwang, Sang-Joon Kim, Chung-Gyu Park, Seong Hoe Park
BACKGROUND: Pig islet xenotransplantation is a promising alternative to allogeneic transplantation. However, the wide immunologic barrier between pigs and primates limits the long-term survival of the graft. MD-3, a novel monoclonal antibody (mAb) that recognizes a particular epitope of human ICAM-1, can render T cells tolerant to a xenograft by arresting dendritic cell maturation. We report the long-term survival of adult wild-type pig islets and successful retransplantation in nonhuman primates using a protocol comprising induction with MD-3 mAb and maintenance with anti-CD154 mAb and sirolimus...
November 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29130360/autophagy-and-innate-immunity-insights-from-invertebrate-model-organisms
#17
Cheng-Ju Kuo, Malene Hansen, Emily Troemel
Macroautophagy/autophagy is a fundamental intracellular degradation process with multiple roles in immunity, including direct elimination of intracellular microorganisms via 'xenophagy.' In this review, we summarize studies from the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans that highlight the roles of autophagy in innate immune responses to viral, bacterial, and fungal pathogens. Research from these genetically tractable invertebrates has uncovered several conserved immunological paradigms, such as direct targeting of intracellular pathogens by xenophagy and regulation of autophagy by pattern recognition receptors in D...
November 13, 2017: Autophagy
https://www.readbyqxmd.com/read/29128670/synchronous-immune-alterations-mirror-clinical-response-during-allergen-immunotherapy
#18
Amedee Renand, Mohamed H Shamji, Kristina M Harris, Tielin Qin, Erik Wambre, Guy W Scadding, Peter A Wurtzen, Stephen J Till, Alkis Togias, Gerald T Nepom, William W Kwok, Stephen R Durham
BACKGROUND: Three years treatment with either sublingual or subcutaneous allergen immunotherapy has been shown to be effective and to induce long-term tolerance. The GRASS(∗) trial demonstrated that two years treatment via either route was effective in suppressing the response to nasal allergen challenge, although was insufficient for inhibition one year after discontinuation. OBJECTIVE: To examine in the GRASS trial the time-course of immunologic changes during two years sublingual and subcutaneous immunotherapy and for one year after treatment discontinuation...
November 8, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29127996/highlights-in-immune-response-microbiome-and-precision-medicine-in-allergic-disease-and-asthma
#19
EDITORIAL
Milena Sokolowska, Cezmi A Akdis
Several recent key findings in immunology of allergic diseases that have led to a need of reassessment of our current thinking are reviewed in this issue of the journal. Recently developed strong evidence on the role of hygiene hypothesis in protection from allergic disease and its immune mechanisms is reviewed by Ober et al. The authors pointed out immunologic mechanisms of lower prevalence of asthma and allergic sensitization observed among Amish children living on traditional farms with higher endotoxin levels as compared to Hutterite children living on industrialized farms...
October 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29124456/serial-immunological-parameters-in-a-phase-ii-trial-of-exemestane-and-low-dose-oral-cyclophosphamide-in-advanced-hormone-receptor-positive-breast-cancer
#20
Maryann Kwa, Xiaochun Li, Yelena Novik, Ruth Oratz, Komal Jhaveri, Jennifer Wu, Ping Gu, Marleen Meyers, Franco Muggia, James Speyer, Alyssa Iwano, Maryam Bonakdar, Lina Kozhaya, Ece Tavukcuoglu, Bahar Budan, Roy Raad, Judith D Goldberg, Derya Unutmaz, Sylvia Adams
BACKGROUND AND PURPOSE: Resistance to endocrine therapies in hormone receptor (HR)-positive breast cancer is a significant challenge. Prior studies have shown that low-dose oral cyclophosphamide can transiently deplete regulatory T cells (Tregs) and improve anti-tumor immunity. We investigated the combination of exemestane with cyclophosphamide in patients with advanced HR-positive breast cancer and assessed changes in circulating immune cell subsets. METHODS: This was a single-arm phase II trial of exemestane with cyclophosphamide in patients with metastatic HR-positive/HER2-negative breast cancer who had progressed on prior endocrine therapy (ClinicalTrials...
November 9, 2017: Breast Cancer Research and Treatment
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