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https://www.readbyqxmd.com/read/27914063/episweep-computationally-driven-reengineering-of-therapeutic-proteins-to-reduce-immunogenicity-while-maintaining-function
#1
Yoonjoo Choi, Deeptak Verma, Karl E Griswold, Chris Bailey-Kellogg
Therapeutic proteins are yielding ever more advanced and efficacious new drugs, but the biological origins of these highly effective therapeutics render them subject to immune surveillance within the patient's body. When recognized by the immune system as a foreign agent, protein drugs elicit a coordinated response that can manifest a range of clinical complications including rapid drug clearance, loss of functionality and efficacy, delayed infusion-like allergic reactions, more serious anaphylactic shock, and even induced auto-immunity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27896329/myasthenia-gravis-with-acute-respiratory-failure-in-the-emergency-department
#2
Hasan Huseyin Kozak, Ali Ulvi Uca, Turgut Teke, Mustafa Altas, Emine Karatas
Acute respiratory failure (ARF) is defined as a sudden malfunction in the ability of respiratory system to maintain adequate gas exchange. Acute hypercapnic respiratory failure develops as a result of ventilation deficiency and it is defined as an increase of PaCO2 above 45 mmHg. Myasthenia Gravis (MG) is a sporadically developing auto-immune deficiency where the neuro-muscular transmission is affected and it is one of the important reasons for neurologically-induced respiratory distress. Here, we report a case of a 75-year-old male patient previously undiagnosed MG, who presented with ARF...
June 2016: Turkish Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27880975/ror%C3%AE-t-expression-in-tregs-promotes-systemic-lupus-erythematosus-via-il-17-secretion-alteration-of-treg-phenotype-and-suppression-of-th2-responses
#3
Malte A Kluger, Anna Nosko, Torben Ramcke, Boeren Goerke, Matthias C Meyer, Claudia Wegscheid, Michael Luig, Gisa Tiegs, Rolf A K Stahl, Oliver M Steinmetz
Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex and poorly understood immuno-pathogenesis. However, a pathogenic role for the Th17 axis was demonstrated by many studies, while Tregs were shown to mediate protection. Recently, we and others characterized a novel and independent T cell population expressing both, the Treg characteristic transcription factor Foxp3 and the Th17 defining RORγt. Studies in a model of acute glomerulonephritis unveiled potent regulatory, but in addition also pro-inflammatory functions of RORγt(+) Foxp3(+) Tregs...
November 23, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27866769/modular-virus-like-particles-for-sublingual-vaccination-against-group-a-streptococcus
#4
Arjun Seth, Il Gyu Kong, Su-Hyun Lee, Jin-Young Yang, Yong-Soo Lee, Yeji Kim, Nani Wibowo, Anton P J Middelberg, Linda H L Lua, Mi-Na Kweon
Infection with Group A streptococcus (GAS)-an oropharyngeal pathogen-leads to mortality and morbidity, primarily among developing countries and indigenous populations in developed countries. The development of safe and affordable GAS vaccines is challenging, due to the presence of various unique GAS serotypes, antigenic variation within the same serotype, and potential auto-immune responses. In the present study, we evaluated the use of a sublingual freeze-dried (FD) formulation based on immunogenic modular virus-like particles (VLPs) carrying the J8 peptide (J8-VLPs) as a potential safe and cost-effective GAS vaccine for inducing protective systemic and mucosal immunity...
December 12, 2016: Vaccine
https://www.readbyqxmd.com/read/27805845/presence-of-auto-reactive-mhc-class-i-restricted-calcium-sensing-receptor-casr-specific-cd8-t-cells-in-idiopathic-hypoparathyroidism
#5
Samrina Mahtab, Utpreksha Vaish, Soma Saha, Archana Singh, Ravinder Goswami, Rajni Rani
CONTEXT: Autoimmunity to Calcium sensing receptor (CaSR) has been implicated in aetiopathogenesis of Idiopathic hypoparathyroidism (IH). While humoral immune responses have been shown, cell mediated auto-immune responses have not been demonstrated. OBJECTIVE: To study CaSR specific cytotoxic T cell responses in PBMCs of IH patients. DESIGN: Twenty four peptides of CaSR (RH1-RH24) were evaluated for their ex-vivo potential to stimulate PBMCs from IH patients and controls in IFN-γ ELISPOT assays...
November 2, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27743827/-plasmapheresis-failure-in-the-treatment-of-auto-immune-pulmonary-alveolar-proteinosis
#6
A Jézéquel, M Kerjouan, M Lederlin, C Lainé-Caroff, C Camus, P Delaval, S Jouneau
INTRODUCTION: Auto-immune pulmonary alveolar proteinosis is a rare disorder characterized by the accumulation of surfactant proteins in the alveoli. CASE REPORT: We report a case of a 41-year-old smoker, presenting initially with acute respiratory failure. Whole lung lavages were effective initially but only for a few weeks. GM-CSF subcutaneous injections were not effective, and then plasmapheresis were tried. CONCLUSION: This is the fifth report of the use of this treatment in auto-immune pulmonary alveolar proteinosis...
October 13, 2016: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/27727326/the-biophysical-characterisation-and-saxs-analysis-of-human-nlrp1-uncover-a-new-level-of-complexity-of-nlr-proteins
#7
Luigi Martino, Louise Holland, Evangelos Christodoulou, Simone Kunzelmann, Diego Esposito, Katrin Rittinger
NOD-like receptors represent an important class of germline-encoded pattern recognition receptors that play key roles in the regulation of inflammatory signalling pathways. They function as danger sensors and initiate inflammatory responses and the production of cytokines. Since NLR malfunction results in chronic inflammation and auto-immune diseases, there is a great interest in understanding how they work on a molecular level. To date, a lot of insight into the biological functions of NLRs is available but biophysical and structural studies have been hampered by the difficulty to produce soluble and stable recombinant NLR proteins...
2016: PloS One
https://www.readbyqxmd.com/read/27708618/the-underexploited-role-of-non-coding-rnas-in-lysosomal-storage-diseases
#8
Matheus Trovão Queiroz, Vanessa Gonçalves Pereira, Cinthia Castro do Nascimento, Vânia D'Almeida
Non-coding RNAs (ncRNAs) are a functional class of RNA involved in the regulation of several cellular processes which may modulate disease onset, progression, and prognosis. Lysosomal storage diseases (LSD) are a group of rare disorders caused by mutations of genes encoding specific hydrolases or non-enzymatic proteins, characterized by a wide spectrum of manifestations. The alteration of ncRNA levels is well established in several human diseases such as cancer and auto-immune disorders; however, there is a lack of information focused on the role of ncRNA in rare diseases...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27696475/a-randomized-and-double-blind-controlled-trial-evaluating-the-safety-and-efficacy-of-rituximab-for-warm-auto-immune-hemolytic-anemia-in-adults-the-raiha-study
#9
Marc Michel, Louis Terriou, Francoise Roudot-Thoraval, Mohamed Hamidou, Mikael Ebbo, Guillaume Le Guenno, Lionel Galicier, Sylvain Audia, Bruno Royer, Anne-Sophie Morin, Jean Marie Michot, Arnaud Jaccard, Laurent Frenzel, Mehdi Khellaf, Bertrand Godeau
This Phase 3 multicentre randomized double-blind and placebo-controlled trial aimed to compare the efficacy and safety of rituximab (RTX) to placebo for treating newly diagnosed warm autoimmune hemolytic anemia (wAIHA) in adults receiving prednisone. Adults with a confirmed diagnosis of wAIHA who previously received corticosteroids for less than 6 weeks could be included. At inclusion, all patients received prednisone at a daily dose of 1 mg/kg for 2 weeks, and then tapered according to a pre-defined recommended reduction scheme...
October 3, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27694218/exercise-induced-brachial-artery-blood-flow-and-vascular-function-is-impaired-in-systemic-sclerosis
#10
Daniel R Machin, Heather L Clifton, Ryan S Garten, Jayson R Gifford, Russell S Richardson, D Walter Wray, Tracy M Frech, Anthony J Donato
Systemic sclerosis (SSc) is a rare autoimmune disease characterized by debilitating fibrosis and vascular dysfunction; however, little is known about the circulatory response to exercise in this population. Therefore, we examined the peripheral hemodynamic and vasodilatory responses to handgrip exercise in 10 patients with SSc (61 ± 4 yr) and 15 age-matched healthy controls (56 ± 5 yr). Brachial artery diameter, blood flow, and mean arterial pressure (MAP) were determined at rest and during progressive static-intermittent handgrip exercise...
December 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27692613/-membranous-nephropathy-diagnosis-new-insights-in-pathophysiology-and-therapeutic-approach
#11
K Dahan
Membranous nephropathy (MN) accounts for about 20% of cases of nephrotic syndrome in the adult. Thickening of glomerular capillary walls results from subepithelial formation of immune deposits containing IgG and the membrane attack complex of complement, which is the major mediator of proteinuria, and antigens. Idiopathic forms of MN (IMN) represent 70 to 80% of all cases. A major breakthrough was the identification of the podocyte antigen PLA2R as the target of circulating antibodies in about 70% of IMN, which confirmed that the disease was auto-immune in nature...
May 25, 2016: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/27688114/autophagy-a-boon-or-bane-in-oral-cancer
#12
REVIEW
Namrata Adhauliya, Anupama N Kalappanavar, I M Ali, Rajeshwari G Annigeri
Autophagy is a catabolic process involving cellular recycling and is believed to play a distinct role in cell survival especially when exposed to stressors, rendering it comparable to the elixir sustaining life. It plays a significant role in various conditions like cancers, neuropathies, heart diseases, auto-immune diseases, etc. Its role in tumorigenesis and cancer therapeutics is worth exploring. Autophagy is believed to help in survival and longevity of cancer cells by buffering metabolic stress. Inhibition of autophagy in an environment of nutrient deprivation leads to cell death...
October 2016: Oral Oncology
https://www.readbyqxmd.com/read/27686032/-beware-polyarteritis-nodosa-still-exists-in-nephrology
#13
Justine Perrin, Julien Carvelli, Bertrand Gondouin, Laurent Daniel, Megan Fraisse, Céline Gaudon, Fouad Bouzana, Henri Vacher-Coponat, Julie Moussi-Francès, Bertrand Dussol, Noémie Jourde-Chiche
Renal involvement of systemic vasculitides is an emergency in nephrology. Although it has become very rare, the diagnosis of polyarteritis nodosa must be considered in some patients. A 70-year-old patient, previously healthy, presented with acute renal failure and malignant hypertension and abundant albuminuria. Subcutaneous nodule, orchitis and mononeuritis appeared subsequently. The search for auto-immunity or viral infection was negative. Markers of thrombotic microangiopathy, present initially, resolved after blood pressure control...
September 24, 2016: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/27684284/inflammasome-derived-exosomes-activate-nf-%C3%AE%C2%BAb-signaling-in-macrophages
#14
Yuehui Zhang, Fangbing Liu, Yanzhi Yuan, Chaozhi Jin, Cheng Chang, Yunping Zhu, Xiuyuan Zhang, Chunyan Tian, Fuchu He, Jian Wang
Exosomes are secreted small vesicles that mediate various biological processes, such as tumorigenesis and immune response. However, whether the inflammasome signaling leads to the change of constituent of exosomes and its roles in immune response remains to be determined. We isolated the exosomes from macrophages with treatment of mock, endotoxin, or endotoxin/nigericin. A label-free quantification method by MS/MS was used to identify the components of exosomes. In total, 2331 proteins were identified and 513 proteins were exclusively detected in exosomes with endotoxin and nigericin treatment...
October 12, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27683036/proteomic-analysis-uncovers-common-effects-of-ifn-%C3%AE-and-il-27-on-the-hla-class-i-antigen-presentation-machinery-in-human-cancer-cells
#15
Andrea Petretto, Grazia Carbotti, Elvira Inglese, Chiara Lavarello, Maria Pia Pistillo, Valentina Rigo, Michela Croce, Luca Longo, Stefania Martini, Paola Vacca, Silvano Ferrini, Marina Fabbi
IL-27, a member of the IL-12-family of cytokines, has shown anti-tumor activity in several pre-clinical models due to anti-proliferative, anti-angiogenic and immune-enhancing effects. On the other hand, IL-27 demonstrated immune regulatory activities and inhibition of auto-immunity in mouse models. Also, we reported that IL-27, similar to IFN-γ, induces the expression of IL-18BP, IDO and PD-L1 immune regulatory molecules in human cancer cells. Here, a proteomic analysis reveals that IL-27 and IFN-γ display a broad overlap of functions on human ovarian cancer cells...
September 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27678376/peripheral-blood-neutrophil-extracellular-trap-production-and-degradation-in-chronic-periodontitis
#16
Phillipa White, Dimitra Sakellari, Helen Roberts, Idyli Risafi, Martin Ling, Paul Cooper, Mike Milward, Iain Chapple
AIMS: To investigate ex vivo peripheral neutrophil extracellular trap (NET) production and their subsequent degradation by plasma in chronic periodontitis patients, and periodontally and systemically healthy-matched controls. MATERIALS AND METHODS: Chronic periodontitis patient and control (n = 40 pairs) peripheral blood neutrophils (PBN) were stimulated for NET quantification. A subset of patients received non-surgical periodontal therapy (n = 19) and NETs were quantified 3 months later alongside controls...
September 28, 2016: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/27652231/post-orgasmic-illness-syndrome-pois
#17
REVIEW
Marcel D Waldinger
Men with post orgasmic illness syndrome (POIS) become ill rather immediately after ejaculation, whether spontaneously at night, during sexual intercourse or masturbation. Two subtypes are distinguished: primary and secondary POIS. It also occurs before or after a man has been sterilized. POIS is an invalidating most probably auto-immune disease leading to much distress in males and their partners. It is characterized by five criteria. Its symptoms are described by seven clusters. However, the manifestation of these symptoms varies from one male to the other but is relatively constant in the person himself...
August 2016: Translational Andrology and Urology
https://www.readbyqxmd.com/read/27643643/concepts-in-mature-t-cell-lymphomas-highlights-from-an-international-joint-symposium-on-t-cell-immunology-and-oncology
#18
Marco Herling, Benjamin Rengstl, René Scholtysik, Sylvia Hartmann, Ralf Küppers, Martin-Leo Hansmann, Hans H Diebner, Ingo Roeder, Hinrich Abken, Sebastian Newrzela, Jörg Kirberg
Growing attention in mature T-cell lymphomas/leukemias (MTCL) is committed to more accurate and meaningful classifications, improved pathogenetic concepts and expanded therapeutic options. This requires considerations of the immunologic concepts of T-cell homeostasis and the specifics of T-cell receptor (TCR) affinities and signaling. Scientists from various disciplines established the CONTROL-T research unit and in an international conference on MTCL they brought together experts from T-cell immunity, oncology, immunotherapy and systems biology...
September 19, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27639114/aqueous-synthesized-quantum-dots-interfere-with-the-nf-%C3%AE%C2%BAb-pathway-and-confer-anti-tumor-anti-viral-and-anti-inflammatory-effects
#19
Zhilin Hu, Bin Song, Lei Xu, Yiling Zhong, Fei Peng, Xiaoyuan Ji, Fang Zhu, Chengkui Yang, Jinying Zhou, Yuanyuan Su, Suning Chen, Yao He, Sudan He
The NF-κB pathway plays crucial roles in inflammatory responses and cell survival. Aberrant constitutive NF-κB activation is associated with various human diseases including cancer and inflammatory and auto-immune diseases. Consequently, it is highly desirable to develop new kinds of inhibitors, which are highly efficacious for blocking the NF-κB pathway. In this study, by using a typical kind of aqueous synthesized quantum dots (QDs), i.e., CdTe QDs, as a model, we for the first time demonstrated that the QDs could selectively affect the cellular nuclear factor-κB (NF-κB) signaling pathway, but do not affect the AKT or ERK pathways...
November 2016: Biomaterials
https://www.readbyqxmd.com/read/27634186/the-role-of-microbiota-and-intestinal-permeability-in-the-pathophysiology-of-autoimmune-and-neuroimmune-processes-with-an-emphasis-on-inflammatory-bowel-disease-type-1-diabetes-and-chronic-fatigue-syndrome
#20
Gerwyn Morris, Michael Berk, André F Carvalho, Javier R Caso, Yolanda Sanz, Michael Maes
BACKGROUND: In steady state conditions intestinal immune homeostasis is maintained by a sophisticated bidirectional dialogue between the microbiota and the intestinal immune system. This "cross talk" is enabled by the presence of highly adapted secretory cells, sampling cells and pattern recognition receptors in the gastric epithelium. METHODS: Herein we discuss the mechanisms involved in the breakdown of intestinal homeostasis and the development of systemic immune activation and neuroinflammation with a view to discussing the importance of these processes, in tandem with genetic and environmental factors, in the pathophysiology of (auto)immune diseases...
September 14, 2016: Current Pharmaceutical Design
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