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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/27912911/hesperidin-ameliorates-immunological-outcome-and-reduces-neuroinflammation-in-the-mouse-model-of-multiple-sclerosis
#2
Dariush Haghmorad, Mohammad Bagher Mahmoudi, Zohreh Salehipour, Zoleikha Jalayer, Amir Abbas Momtazi Brojeni, Maryam Rastin, Parviz Kokhaei, Mahmoud Mahmoudi
Multiple sclerosis (MS) is the most abundant central nervous system (CNS) inflammatory disease, which is due to the reaction of auto reactive T cells with own myelin proteins, leading to physical disorder and paralysis among people suffering the disease. Hesperidin, a flavanone glycoside found abundantly in citrus fruits possesses a wide range of pharmacological properties including potential anti-inflammatory and anti-cancer effects. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of hesperidin on MS alleviation...
November 26, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27903991/role-of-oxidative-stress-and-inflammatory-factors-in-diabetic-kidney-disease
#3
Esmat Aghadavod, Samaneh Khodadadi, Azar Baradaran, Parto Nasri, Mahmood Bahmani, Mahmoud Rafieian-Kopaei
Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and its prevalence has been increasing in developed countries. Diabetic nephropathy has become the most common single cause of end-stage renal disease worldwide. Oxidative stress and inflammation factors are hypothesized to play a role in the development of late diabetes complications. Chronic hyperglycemia increases oxidative stress, significantly modifies the structure and function of proteins and lipids, and induces glycoxidation and peroxidation...
November 2016: Iranian Journal of Kidney Diseases
https://www.readbyqxmd.com/read/27896829/immunomodulatory-and-immunosuppressive-roles-of-1%C3%AE-25-oh-2d3-in-autoimmune-diseases
#4
REVIEW
Hussaini Alhassan Mohammed, Ali Akbar Saboor-Yaraghi, Abbas Mirshafiey, Haumayon Vahedi, Mohammad Reza Shiri-Shahsavar, Ateke Mousavi Nasl Khameneh
BACKGROUND: Autoimmune diseases are pathological conditions characterized by abnormal. responses, accompanied by auto-antibodies to self-molecules. The roles vitamin D in autoimmune diseases has increased significantly in the recent past from its functions in calcium and phosphate homeostasis, it is now involved in the regulations and proliferations of Th1 and Th17 lymphocyte. 1α,25(OH)2D3 in very important in ameliorations of inflammatory disorders arising from autoimmune diseases, but the mechanism by which this is done is still a bone of contentions...
November 29, 2016: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27896624/autologous-bone-marrow-stem-cell-transplantation-for-the-treatment-of-ulcerative-colitis-complicated-with-herpes-zoster-a-case-report
#5
Hang Xiang, Xiaomei Zhang, Chao Yang, Wenhuan Xu, Xin Ge, Rong Zhang, Ya Qiu, Wanjun Sun, Fan Li, Tianyuan Xiang, Haixu Chen, Zheng Wang, Qiang Zeng
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with continuous or recurrent symptoms. A 42-year-old male patient with intermittent diarrhea accompanied by bloody mucopurulent stools was admitted to our hospital. The diagnosis of UC was confirmed by a combination of laboratory examination, colonoscopy, and histological assay. The patient developed herpes zoster in the hospital, which challenged traditional treatments. Therefore, we performed an autologous bone marrow cells to modulate the immune system with his permission...
November 28, 2016: Frontiers of Medicine
https://www.readbyqxmd.com/read/27896329/myasthenia-gravis-with-acute-respiratory-failure-in-the-emergency-department
#6
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/27884543/immunometabolism-is-it-under-the-eye-of-the-clock
#7
REVIEW
James O Early, Anne M Curtis
Molecular clocks allow an organism to track time of day, providing the means to anticipate and respond to the daily changes within the environment. In mammals the molecular clock consists of a network of proteins that form auto-regulatory feedback loops that drive rhythms in physiology and behavior. In recent times the extent to which the molecular clock controls key metabolic and immune pathways has begun to emerge. For example, the main clock protein BMAL1 has been linked to mitochondrial metabolism, mitochondrial dynamics and various host defense pathways...
November 21, 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27883079/a-parasite-derived-68-mer-peptide-ameliorates-autoimmune-disease-in-murine-models-of-type-1-diabetes-and-multiple-sclerosis
#8
Maria E Lund, Judith Greer, Aakanksha Dixit, Raquel Alvarado, Padraig McCauley-Winter, Joyce To, Akane Tanaka, Andrew T Hutchinson, Mark W Robinson, Ann M Simpson, Bronwyn A O'Brien, John P Dalton, Sheila Donnelly
Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines...
November 24, 2016: Scientific Reports
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
#9
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
#10
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/27864925/drug-induced-pyoderma-gangrenosum-a-model-to-understand-the-pathogenesis-of-pyoderma-gangrenosum
#11
REVIEW
B C Wu, E D Patel, A G Ortega-Loayza
Pyoderma gangrenosum (PG) is a rare auto-inflammatory condition in which the alteration of neutrophil function and the innate immune response play key roles in its pathogenesis. Cases of PG have been reported in patients being treated with certain medications, which may help us to understand some of the possible pathways involved in the etiology of PG. The aim of this review is to review the cases of PG triggered by certain drugs and try to thoroughly understand the pathogenesis of the disease. To accomplish this, a PubMed search was completed using the following words: pyoderma gangrenosum, neutrophilic dermatosis, pathophysiology, drug-induced pyoderma gangrenosum...
November 19, 2016: British Journal of Dermatology
https://www.readbyqxmd.com/read/27863820/b-cell-depleting-therapy-regulates-splenic-and-circulating-t-follicular-helper-cells-in-immune-thrombocytopenia
#12
Sylvain Audia, Marzia Rossato, Malika Trad, Maxime Samson, Kim Santegoets, Alexandrine Gautheron, Cornelis Bekker, Olivier Facy, Nicolas Cheynel, Pablo Ortega-Deballon, Mathieu Boulin, Sabine Berthier, Vanessa Leguy-Seguin, Laurent Martin, Marion Ciudad, Nona Janikashvili, Philippe Saas, Timothy Radstake, Bernard Bonnotte
B cells are involved in immune thrombocytopenia (ITP) pathophysiology by producing antiplatelet auto-antibodies. However more than a half of ITP patients do not respond to B cell depletion induced by rituximab (RTX). The persistence of splenic T follicular helper cells (TFH) that we demonstrated to be expanded during ITP and to support B cell differentiation and antiplatelet antibody-production may participate to RTX inefficiency. Whereas it is well established that the survival of TFH depends on B cells in animal models, nothing is known in humans yet...
November 15, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27856208/randomized-comparison-of-allogeneic-vs-autologous-mesenchymal-stem-cells-for-non-lschemic-dilated-cardiomyopathy-poseidon-dcm-trial
#13
Joshua M Hare, Darcy L DiFede, Angela M Castellanos, Victoria Florea, Ana M Landin, Jill El-Khorazaty, Aisha Khan, Muzammil Mushtaq, Maureen H Lowery, John J Byrnes, Robert C Hendel, Mauricio G Cohen, Carlos E Alfonso, Krystalenia Valasaki, Marietsy V Pujol, Samuel Golpanian, Eduard Ghersin, Joel E Fishman, Pradip Pattany, Samirah A Gomes, Cindy Delgado, Roberto Miki, Fouad Abuzeid, Mayra Vidro-Casiano, Courtney Premer, Audrey Medina, Valeria Porras, Konstantinos E Hatzistergos, Erica Anderson, Adam Mendizabal, Raul Mitrani, Alan W Heldman
BACKGROUND: While human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic non-ischemic dilated cardiomyopathy (NIDCM). OBJECTIVES: The POSEIDON-DCM trial is a randomized comparison of safety and efficacy of autologous (auto) vs. allogeneic (allo) bone marrow-derived hMSCs in NIDCM. METHODS: Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital...
November 14, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27834858/impact-of-microbes-on-the-pathogenesis-of-primary-biliary-cirrhosis-pbc-and-primary-sclerosing-cholangitis-psc
#14
REVIEW
Jochen Mattner
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent the major clinical entities of chronic cholestatic liver diseases. Both disorders are characterized by portal inflammation and slowly progress to obliterative fibrosis and eventually liver cirrhosis. Although immune-pathogenic mechanisms have been implicated in the pathogenesis of PBC and PSC, neither disorder is considered to be a classical autoimmune disease, as PSC and PBC patients do not respond to immune-suppressants. Furthermore, the decreased bile flow resulting from the immune-mediated tissue assault and the subsequent accumulation of toxic bile products in PBC and PSC not only perpetuates biliary epithelial damage, but also alters the composition of the intestinal and biliary microbiota and its mutual interactions with the host...
November 9, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27833025/endogenous-polyclonal-anti-il-1-antibody-responses-potentiate-il-1-activity-during-pathogenic-inflammation
#15
Gunther Spohn, Natalia Arenas-Ramirez, Gregory Bouchaud, Onur Boyman
BACKGROUND: Particular neutralizing monoclonal antibodies to certain cytokines act as agonists in vivo by protection of the cytokine's active site and prolongation of cytokine half-life. While this principle might be useful for targeted immunotherapy, its role in the pathogenesis of inflammation and autoimmunity is unclear. OBJECTIVE: We sought to determine whether slight, structurally non-relevant modifications of the prototypic pro-inflammatory cytokine interleukin-1β (IL-1β) during an immune response could elicit polyclonal anti-IL-1β antibody responses that modulated IL-1β's in vivo activity...
November 7, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27832210/gm-csf-producing-th-cells-in-rats-sensitive-and-resistant-to-experimental-autoimmune-encephalomyelitis
#16
Zorica Stojić-Vukanić, Ivan Pilipović, Ivana Vujnović, Mirjana Nacka-Aleksić, Raisa Petrović, Nevena Arsenović-Ranin, Mirjana Dimitrijević, Gordana Leposavić
Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment...
2016: PloS One
https://www.readbyqxmd.com/read/27821860/identification-of-novel-hla-a-0201-restricted-ctl-epitopes-in-chinese-vitiligo-patients
#17
Tingting Cui, Xiuli Yi, Sen Guo, Fubo Zhou, Ling Liu, Chunying Li, Kai Li, Tianwen Gao
Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair. Recent studies suggested the key role of CD8(+)T lymphocytes for mediating immune response in vitiligo through melanocyte differentiation antigens, including tyrosinase, gp100 and MelanA/Mart-1. However, the specific epitopes of these auto-antigens are still unknown. In our study, we predicted the possible HLA-A*0201-restricted nonapeptides overlaying the full-length amino acid sequences of these three known antigens and investigated the lymphocytes reactivity to these nonapeptides by Elispot assay...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27821286/immunization-against-lysozyme-like-proteins-affect-sperm-function-and-fertility-in-the-rat
#18
Ganapathy Narmadha, Suresh Yenugu
Proteins of the epididymal and testicular mileu contribute to sperm maturation and a vast majority of them remain uncharacterised. In this study, the role of three Lysozyme-like (LYZL) proteins, namely LYZL1, LYZL4 and LYZL6 in sperm function was assessed using in vitro neutralization and auto antibodies generation model. Rats immunized with LYZL1, LYZL4 and LYZL6 proteins had a litter size of 5.93, 8.47 and 2.10 respectively compared to 9.96 in the control rats. The litter size was further reduced to 4.53, 7...
November 2, 2016: Journal of Reproductive Immunology
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
#19
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/27803386/characterization-of-isoniazid-specific-t-cell-clones-in-patients-with-anti-tuberculosis-drug-related-liver-and-skin-injury
#20
Toru Usui, Xiaoli Meng, Katy Saide, John Farrell, Paul Thomson, Paul Whitaker, John Watson, Neil S French, B Kevin Park, Dean J Naisbitt
Isoniazid, rifampicin, pyrazinamide and ethambutol are commonly used for the treatment of tuberculosis. Drug exposure is occasionally associated with liver and/or skin injury. The aim of this study was to determine whether drug-specific T-cells are detectable in patients with adverse reactions and if so characterize the nature of the T-cell response. PBMC from 6 patients with anti-tuberculosis drug-related adverse reactions (4 liver, 2 skin) were used to detect drug-responsive T-lymphocytes. Positive lymphocyte transformation test and/or ELIspot results were observed with all 6 patients...
November 1, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
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