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"Immune tolerance"

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https://www.readbyqxmd.com/read/28817385/novel-molecular-defects-associated-with-very-early-onset-inflammatory-bowel
#1
Sara Ciullini Mannurita, Eleonora Gambineri
PURPOSE OF REVIEW: Immune dysregulation disorders present with common clinical features of multiorgan autoimmunity. Gastrointestinal involvement is the hallmark of an impaired immune homeostasis. This review will give an overview on the novel phenotypes, highlighting the major points that will help to enable early diagnosis and treatment. RECENT FINDINGS: The rapid progress on DNA sequencing technologies have led to the identification of monogenic defects that adversely impact the control of immune homeostasis...
August 16, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28816955/serum-hbeag-and-hbv-dna-levels-are-not-always-proportional-and-only-high-levels-of-hbeag-most-likely-correlate-with-high-levels-of-hbv-dna-a-community-based-study
#2
Ping Chen, Qinfen Xie, Xuan Lu, Chengbo Yu, Kaijin Xu, Bing Ruan, Hongcui Cao, Hainv Gao, Lanjuan Li
This study aimed to investigate the correlation between quantitative hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels, and to determine whether semiquantitative measurement of HBeAg can indicate the extent of HBV replication in HBeAg-positive subjects in the immune tolerant phase.A cross-sectional, community-based survey was carried out in 12 communities of 2 counties in Zhejiang Province, China. A panel of 788 HBeAg-positive subjects was divided into 4 groups according to HBV DNA level...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28814660/sustained-immune-tolerance-induction-in-enzyme-replacement-therapy-treated-crim-negative-patients-with-infantile-pompe-disease
#3
Zoheb B Kazi, Ankit K Desai, Kathryn L Berrier, R Bradley Troxler, Raymond Y Wang, Omar A Abdul-Rahman, Pranoot Tanpaiboon, Nancy J Mendelsohn, Eli Herskovitz, David Kronn, Michal Inbar-Feigenberg, Catherine Ward-Melver, Michelle Polan, Punita Gupta, Amy S Rosenberg, Priya S Kishnani
BACKGROUND: Cross-reactive immunological material-negative (CRIM-negative) infantile Pompe disease (IPD) patients develop an immune response against enzyme replacement therapy (ERT) with alglucosidase alfa that nullifies ERT efficacy. Prophylactic immune tolerance induction (ITI) with rituximab, methotrexate, and IVIG successfully prevents development of deleterious rhGAA IgG antibodies; however, safety, likelihood of success, and long-term efficacy of ITI in a larger cohort remain unknown...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28812775/polymorphic-light-eruption-and-il-1-family-members-any-difference-with-allergic-contact-dermatitis
#4
S Lembo, G Caiazzo, N Balato, G Monfrecola, V Patra, P Wolf, A Balato
Polymorphic light eruption (PLE) is described as a delayed-type hypersensitivity reaction (DTHR) toward a de novo light-induced antigen, yet to be identified. In effect, the inflammatory pathways of PLE and allergic contact dermatitis (ACD) share common patterns in terms of the mediators involved from the innate and adaptive immune system participating in the DTHR. As we have previously highlighted the role of interleukin (IL)-1 family members in ACD, we hypothesised that the same mediators could have similar functions in PLE...
August 16, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28804903/targeting-of-tolerogenic-dendritic-cells-towards-heat-shock-proteins-a-novel-therapeutic-strategy-for-autoimmune-diseases
#5
REVIEW
Manon A A Jansen, Rachel Spiering, Femke Broere, Jacob M van Laar, John D Isaacs, Willem van Eden, Catharien M U Hilkens
Tolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. The rationale of using tolDCs is that they can specifically target the pathogenic T cell response, while leaving other, protective T cell responses intact. Several ways of generating therapeutic tolDCs have been described, but whether these tolDCs should be loaded with autoantigen(s), and if so, with which autoantigen(s), remains unclear. Autoimmune diseases, such as rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen...
August 14, 2017: Immunology
https://www.readbyqxmd.com/read/28803690/new-insights-into-non-conventional-epitopes-as-t-cell-targets-the-missing-link-for-breaking-immune-tolerance-in-autoimmune-disease
#6
REVIEW
James Harbige, Martin Eichmann, Mark Peakman
The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases...
August 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28803660/multiple-sclerosis-skin-induced-antigen-specific-immune-tolerance
#7
REVIEW
Paula Wildner, Krzysztof W Selmaj
Multiple sclerosis (MS) is a highly prevalent demyelinating disorder, presumed to be driven by an autoimmune response toward the central nervous system (CNS) components. All currently available treatments modulate the immune system globally and besides the reduction of disease activity, they may also impose considerable disturbances on the immune protective mechanisms. Thus, induction of antigen-specific immune tolerance remains the ultimate goal of MS therapy. Such approach carries promising therapeutic perspectives and, above all, a desirable safety profile...
August 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28799202/immune-tolerance-induced-by%C3%A2-platelet-targeted-factor-viii-gene-therapy-in-hemophilia-a-mice-is-cd4%C3%A2-t-cell-mediated
#8
Y Chen, X Luo, J A Schroeder, J Chen, C K Baumgartner, J Hu, Q Shi
BACKGROUND: Immune responses are a major concern in gene therapy. Our previous studies demonstrated that platelet-targeted FVIII (2bF8) gene therapy together with in vivo drug-selection of transduced cells can rescue the bleeding diathesis and induce immune tolerance in FVIII(null) mice. OBJECTIVE: To investigate whether non-selectable 2bF8 lentiviral vector (LV) for the induction of platelet-FVIII expression is sufficient to induce immune tolerance and how immune tolerance is induced after 2bF8LV gene therapy...
August 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28798332/absence-of-grail-promotes-cd8-t-cell-anti-tumour-activity
#9
Cara Haymaker, Yi Yang, Junmei Wang, Qiang Zou, Anupama Sahoo, Andrei Alekseev, Divyendu Singh, Krit Ritthipichai, Yared Hailemichael, Oanh N Hoang, Hong Qin, Kimberly S Schluns, Tiejun Wang, Willem W Overwijk, Shao-Cong Sun, Chantale Bernatchez, Larry W Kwak, Sattva S Neelapu, Roza Nurieva
T-cell tolerance is a major obstacle to successful cancer immunotherapy; thus, developing strategies to break immune tolerance is a high priority. Here we show that expression of the E3 ubiquitin ligase Grail is upregulated in CD8(+) T cells that have infiltrated into transplanted lymphoma tumours, and Grail deficiency confers long-term tumour control. Importantly, therapeutic transfer of Grail-deficient CD8(+) T cells is sufficient to repress established tumours. Mechanistically, loss of Grail enhances anti-tumour reactivity and functionality of CD8(+) T cells...
August 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28797733/propagation-of-respiratory-viruses-in-human-airway-epithelia-reveals-persistent-virus-specific-signatures
#10
Manel Essaidi-Laziosi, Francisco Brito, Sacha Benaoudia, Léna Royston, Valeria Cagno, Mélanie Fernandes-Rocha, Isabelle Piuz, Evgeny Zdobnov, Song Huang, Samuel Constant, Marc-Olivier Boldi, Laurent Kaiser, Caroline Tapparel
BACKGROUND: Leading etiologies of acute illnesses, respiratory viruses typically cause self-limited diseases, though severe complications can occur in fragile patients. Rhinoviruses, respiratory enteroviruses, influenza virus, respiratory syncytial viruses and coronaviruses are highly prevalent respiratory pathogens, but due to the lack of reliable animal models, their differential pathogenesis remains poorly characterized. OBJECTIVE: To compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia...
August 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28794283/metabolic-and-immune-effects-of-immunotherapy-with-proinsulin-peptide-in-human-new-onset-type-1-diabetes
#11
Mohammad Alhadj Ali, Yuk-Fun Liu, Sefina Arif, Danijela Tatovic, Hina Shariff, Vivienne B Gibson, Norkhairin Yusuf, Roman Baptista, Martin Eichmann, Nedyalko Petrov, Susanne Heck, Jennie H M Yang, Timothy I M Tree, Irma Pujol-Autonell, Lorraine Yeo, Lucas R Baumard, Rachel Stenson, Alex Howell, Alison Clark, Zoe Boult, Jake Powrie, Laura Adams, Florence S Wong, Stephen Luzio, Gareth Dunseath, Kate Green, Alison O'Keefe, Graham Bayly, Natasha Thorogood, Robert Andrews, Nicola Leech, Frank Joseph, Sunil Nair, Susan Seal, HoYee Cheung, Craig Beam, Robert Hills, Mark Peakman, Colin M Dayan
Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in preclinical disease models. We studied safety and mechanistic effects of injecting human leukocyte antigen-DR4(DRB1*0401)-restricted immunodominant proinsulin peptide intradermally every 2 or 4 weeks for 6 months in newly diagnosed type 1 diabetes patients. Treatment was well tolerated with no systemic or local hypersensitivity. Placebo subjects showed a significant decline in stimulated C-peptide (measuring insulin reserve) at 3, 6, 9, and 12 months versus baseline, whereas no significant change was seen in the 4-weekly peptide group at these time points or the 2-weekly group at 3, 6, and 9 months...
August 9, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28792701/predictive-value-of-hepatitis-b-core-related-antigen-hbcrag-during-the-natural-history-of-hepatitis-b-virus-infection
#12
Yu Gou, Yanhua Zhao, Chenli Rao, Shu Feng, Tingting Wang, Dongdong Li, Chuanmin Tao
BACKGROUND: The natural history of HBV infection includes immune tolerance (IT), immune clearance (IC), HBeAg-negative inactive/quiescent carrier (ENQ), and HBeAg-negative hepatitis (ENH) phases. As the current biomarkers for discriminating the four phases still have some weaknesses, additional serological indicators are needed. Hepatitis B core-related antigen (HBcrAg) encoded with the precore/core gene contains denatured HBeAg, HBV core antigen (HBcAg), and a 22-KDa precore protein (p22cr) and has been demonstrated to have a close association with the natural history of hepatitis B infection...
July 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28792480/the-role-of-nutritional-aspects-in-food-allergy-prevention-and-management
#13
REVIEW
Alessandra Mazzocchi, Carina Venter, Kate Maslin, Carlo Agostoni
The prevalence of food allergy in childhood appears to be increasing in both developed and transitional countries. The aim of this paper is to review and summarise key findings in the prevention and management of food allergy, focusing on the role of dietary components and nutritional habits in the development and optimal functioning of the immune system. Essential fatty acids, zinc and vitamin D are likely to enhance the anti-inflammatory and antioxidative barrier and promote immunologic tolerance. Additionally, nutritional components such as pre- and probiotics represent a novel research approach in the attempt to induce a tolerogenic immune environment...
August 9, 2017: Nutrients
https://www.readbyqxmd.com/read/28792150/immune-tolerance-of-human-dental-pulp-derived-mesenchymal-stem-cells-mediated-by-cd4%C3%A2-%C2%BAcd25%C3%A2-%C2%BAfoxp3%C3%A2-%C2%BA-regulatory-t-cells-and-induced-by-tgf-%C3%AE-1-and-il-10
#14
Jong Won Hong, Jung Hyun Lim, Chooryung J Chung, Tae Jo Kang, Tae Yeon Kim, Young Seok Kim, Tae Suk Roh, Dae Hyun Lew
PURPOSE: Most studies on immune tolerance of mesenchymal stem cells (MSCs) have been performed using MSCs derived from bone marrow, cord blood, or adipose tissue. MSCs also exist in the craniofacial area, specifically in teeth. The purpose of this study was to evaluate the mechanisms of immune tolerance of dental pulp-derived MSC (DP-MSC) in vitro and in vivo. MATERIALS AND METHODS: We isolated DP-MSCs from human dental pulp and co-cultured them with CD4⁺ T-cells...
September 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28791314/generation-of-a-vero-based-packaging-cell-line-to-produce-sv40-gene-delivery-vectors-for-use-in-clinical-gene-therapy-studies
#15
Miguel G Toscano, Jeroen van der Velden, Sybrand van der Werf, Machteld Odijk, Ana Roque, Rafael J Camacho-Garcia, Irene G Herrera-Gomez, Irene Mancini, Peter de Haan
Replication-defective (RD) recombinant simian virus 40 (SV40)-based gene delivery vectors hold a great potential for clinical applications because of their presumed non-immunogenicity and capacity to induce immune tolerance to the transgene products in humans. However, the clinical use of SV40 vectors has been hampered by the lack of a packaging cell line that produces replication-competent (RC) free SV40 particles in the vector production process. To solve this problem, we have adapted the current SV40 vector genome used for the production of vector particles and generated a novel Vero-based packaging cell line named SuperVero that exclusively expresses the SV40 large T antigen...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28790848/the-status-of-immunosuppression-in-patients-with-stage-iiib-or-iv-non-small-cell-lung-cancer-correlates-with-the-clinical-characteristics-and-response-to-chemotherapy
#16
Yuan Wang, Guo-Fang Hu, Zhe-Hai Wang
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (Trp) degradation via the kynurenine (Kyn) pathway, which inhibits the proliferation of T cells and induces the apoptosis of T cells, leading to immune tolerance. Therefore, IDO has been considered as the most important mechanism for tumor cells to escape from immune response. Previous studies suggested that IDO might be involved in the progression of tumor and resistance to chemotherapy. Several preclinical and clinical studies have proven that IDO inhibitors can regulate IDO-mediated tumor immune escape and potentiate the effect of chemotherapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28789525/direct-loading-of-itep-delivered-ctl-epitopes-onto-mhc-class-i-complexes-on-the-dendritic-cell-surface
#17
Shuyun Dong, Peng Wang, Peng Zhao, Mingnan Chen
Cytotoxic T lymphocyte (CTL)-mediated immune responses are the primary defense mechanism against cancer and infection. CTL epitope peptides have been used as vaccines to boost CTL responses; however, the efficacy of these peptides is suboptimal. Under current vaccine formulation and delivery strategies, these vaccines are delivered into and processed inside antigen presenting cells such as dendritic cells (DCs). However, the intracellular process is not efficient, which at least partially contributes to the suboptimal efficacy of the vaccines...
August 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28783689/inhibition-of-hdac8-and-hdac9-by-microbial-short-chain-fatty-acids-breaks-immune-tolerance-of-the-epidermis-to-tlr-ligands
#18
James A Sanford, Ling-Juan Zhang, Michael R Williams, Jon A Gangoiti, Chun-Ming Huang, Richard L Gallo
Epidermal keratinocytes participate in immune defense through their capacity to recognize danger, trigger inflammation, and resist infection. However, normal skin immune function must tolerate contact with an abundant community of commensal microbes without inflammation. We hypothesized that microbial environmental conditions dictate the production of molecules that influence epigenetic events and cause keratinocytes to break innate immune tolerance. Propionibacterium acnes, a commensal skin bacterium, produced the short-chain fatty acids (SCFAs) propionate and valerate when provided a lipid source in hypoxic growth conditions, and these SCFAs inhibited histone deacetylase (HDAC) activity...
October 28, 2016: Science Immunology
https://www.readbyqxmd.com/read/28783671/potent-and-broad-hiv-neutralizing-antibodies-in-memory-b-cells-and-plasma
#19
LaTonya D Williams, Gilad Ofek, Sebastian Schätzle, Jonathan R McDaniel, Xiaozhi Lu, Nathan I Nicely, Liming Wu, Caleb S Lougheed, Todd Bradley, Mark K Louder, Krisha McKee, Robert T Bailer, Sijy O'Dell, Ivelin S Georgiev, Michael S Seaman, Robert J Parks, Dawn J Marshall, Kara Anasti, Guang Yang, Xiaoyan Nie, Nancy L Tumba, Kevin Wiehe, Kshitij Wagh, Bette Korber, Thomas B Kepler, S Munir Alam, Lynn Morris, Gift Kamanga, Myron S Cohen, Mattia Bonsignori, Shi-Mao Xia, David C Montefiori, Garnett Kelsoe, Feng Gao, John R Mascola, M Anthony Moody, Kevin O Saunders, Hua-Xin Liao, Georgia D Tomaras, George Georgiou, Barton F Haynes
Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of distal MPER antibodies and the relationship of memory B cell to plasma bnAbs are poorly understood. HIV-1-specific memory B cell flow sorting and proteomic identification of anti-MPER plasma antibodies from an HIV-1-infected individual were used to isolate broadly neutralizing distal MPER bnAbs of the same B cell clonal lineage...
January 27, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783662/suppression-by-human-foxp3-regulatory-t-cells-requires-foxp3-tip60-interactions
#20
Khalid Bin Dhuban, Eva d'Hennezel, Yasuhiro Nagai, Yan Xiao, Steven Shao, Roman Istomine, Fernando Alvarez, Moshe Ben-Shoshan, Hans Ochs, Bruce Mazer, Bin Li, Chiyoko Sekine, Alan Berezov, Wayne Hancock, Troy R Torgerson, Mark I Greene, Ciriaco A Piccirillo
CD4(+)FOXP3(+) regulatory T (Treg) cells are critical mediators of immune tolerance, and their deficiency owing to FOXP3 mutations in immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) patients results in severe autoimmunity. Different FOXP3 mutations result in a wide range of disease severity, reflecting the relative importance of the affected residues in the integrity of the FOXP3 protein and its various molecular interactions. We characterized the cellular and molecular impact of the most common IPEX mutation, p...
June 16, 2017: Science Immunology
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