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Med Chem. 2017 Sep 6. doi: 10.2174/1573406413666170906121828. [Epub ahead of print]
With the introduction of mAbs the treatment of MS has entered a new era, both with respect to efficacy and target specificity. However, administration of mAbs carries the risk of immune reactions such as acute anaphylaxis, serum sickness a, infection and other autoimmune diseases. In addition, unexpected consequences arise from our incomplete knowledge of the immune system. For example, natalizumab, a monoclonal antibody targeting α4-integrin on leukocytes increases the risk of developing progressive multifocal leukoencephalopathy, without causing notable immunosuppression. Further study on the use of mabs is required, both in vitro and in the clinical field, in order to increase our knowledge upon these new revolutionary therapeutic agents.
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
August 22, 2017 4:32 AM
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Neurological and psychiatric syndromes, collectively referred to as NPSLE, occur frequently in SLE. The frequency of NPSLE varies from 21 to 95%; however, only 13–38% of neuropsychiatric (NP) events could be attributable to SLE in the NPSLE SLICC inception cohort. This variability in the frequency of NPSLE is attributable to the low specificity of the ACR case definitions for SLE-attributed NP syndromes, inclusion of minor NP events in the ACR nomenclature, difficulty in ascertainment of NP events and diverse experience of rheumatologists in the clinical assessment of NP events. Making the correct and early attribution of NP events to SLE is important to institute appropriate immunosuppressive treatment for favourable outcomes. Various attribution models using composite decision rules have been developed and used to ascribe NP events to SLE. This review will focus on the various clinical presentations, diagnostic work-up and attributions of the common NPSLE syndromes, including other NP events not included in the ACR nomenclature but which have come to attention in recent years.
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Gilbert C FAURE
August 16, 2017 8:22 AM
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J Neuroimmunol. 2017 Mar 15;304:35-39. doi: 10.1016/j.jneuroim.2016.05.007. Epub 2016 May 24.
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Gilbert C FAURE
August 12, 2017 3:06 AM
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There is an urgent need in multiple sclerosis (MS) patients to develop biomarkers and laboratory tests to improve early diagnosis, predict clinical relapses, and optimize treatment responses. In healthy individuals, the transport of proteins across the blood-brain barrier (BBB) is tightly regulated; whereas, in MS, CNS inflammation results in damage to neuronal tissues, disruption of BBB integrity, and potential release of neuroinflammatory disease-induced CNS proteins (NDICPs) into CSF and serum. Therefore, changes in serum NDICP abundance could serve as biomarkers of MS. Here we sought to determine if changes in serum NDICPs are detectible prior to clinical onset of experimental autoimmune encephalomyelitis (EAE), and therefore enable prediction of disease onset. Importantly, we show in longitudinal serum specimens from individual mice with EAE, that pre-onset expression waves of SYN2, GS, ENO2, and SYT1 enable prediction of clinical disease with high sensitivity and specificity. Moreover, we observed differences in serum NDICPs between active and passive immunization in EAE, suggested hitherto not appreciated differences for disease induction mechanisms. Our studies provide the first evidence for enabling the prediction of clinical disease using serum NDICPs. The results provide proof-of-concept for the development of high-confidence serum NDICP expression waves and protein biomarker candidates for MS.
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Gilbert C FAURE
August 7, 2017 12:47 PM
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Andrey Rzhetsky and colleagues analyze electronic medical records from over one-third of the US population to estimate disease heritability and to determine the genetic and environmental contributions to disease variance. They obtain 84 new heritability estimates and find that the genetic correlation values for disease pairs differ from their environmental correlation values.
June 27, 2017 A brand new human antibody might quickly turn out to be to be had as a particular medicine for combating common migraine assaults. As showed
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Gilbert C FAURE
August 3, 2017 3:11 PM
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Stem cell‐based therapies for neurodegenerative diseases aim at halting clinical deterioration by regeneration and by providing local support for damaged tissue. Mesenchymal stem cells (MSCs) hol
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Gilbert C FAURE
July 25, 2017 4:18 AM
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High-dimensional, single-cell characterization of the brain's immune compartment Ben Korin, Tamar L Ben-Shaanan, Maya Schiller, Tania Dubovik, Hilla Azulay-Debby, Nadia T Boshnak, Tamar Koren & Asya Rolls AffiliationsContributionsCorresponding author Nature Neuroscience (2017) doi:10.1038/nn.4610
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Gilbert C FAURE
July 19, 2017 6:47 AM
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parkinson T cell alpha synuclein peptides
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Gilbert C FAURE
July 15, 2017 4:07 PM
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The efficacy of B cell depletion therapy in multiple sclerosis indicates their central pathogenic role in disease pathogenesis. The B lymphotropic EBV is a major risk factor in multiple sclerosis, via as yet unclear mechanisms. We reported in a nonhuman primate experimental autoimmune encephalomyelitis model that an EBV-related lymphocryptovirus enables B cells to protect a proteolysis-sensitive immunodominant myelin oligodendrocyte glycoprotein (MOG) epitope (residues 40–48) against destructive processing. This facilitates its cross-presentation to autoaggressive cytotoxic MHC-E–restricted CD8+CD56+ T cells. The present study extends these observations to intact human B cells and identifies a key role of autophagy. EBV infection upregulated APC-related markers on B cells and activated the cross-presentation machinery. Although human MOG protein was degraded less in EBV-infected than in uninfected B cells, induction of cathepsin G activity by EBV led to total degradation of the immunodominant peptides MOG35–55 and MOG1–20. Inhibition of cathepsin G or citrullination of the arginine residue within an LC3-interacting region motif of immunodominant MOG peptides abrogated their degradation. Internalized MOG colocalized with autophagosomes, which can protect from destructive processing. In conclusion, EBV infection switches MOG processing in B cells from destructive to productive and facilitates cross-presentation of disease-relevant epitopes to CD8+ T cells.
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Gilbert C FAURE
July 10, 2017 8:15 AM
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A summary of this report with MedWorm recommendations of related news links and other reading to help further your research.
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Gilbert C FAURE
June 14, 2017 2:39 PM
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Invest Ophthalmol Vis Sci. 2017 Jun 1;58(7):2977-2990. doi: 10.1167/iovs.17-21672.
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Gilbert C FAURE
June 6, 2017 4:43 AM
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This study of combination of genome-wide association data with case-control replication tests the hypothesis that there are common genetic risk variants conveyi
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Gilbert C FAURE
September 1, 2017 2:54 PM
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A new kind of antibody targets a feature shared by proteins thought to cause the most damage in Alzheimer’s disease, Parkinson’s disease, and related conditions, creating potential for a unified treatment approach.
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Gilbert C FAURE
August 18, 2017 2:02 PM
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Lazarevic and colleagues show that T-bet-dependent NKp46+ innate lymphoid cells reside within the meninges of the CNS and initiate meningeal inflammation, thereby facilitating T cell entry into parenchymal CNS tissues and contributing to neuroinflammation.
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Gilbert C FAURE
August 13, 2017 7:37 AM
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J Immunol. 2017 Aug 11. pii: ji1700372. doi: 10.4049/jimmunol.1700372. [Epub ahead of print]
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Gilbert C FAURE
August 8, 2017 8:43 AM
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Alzheimer’s disease (AD) is the leading cause of dementia worldwide. Late-onset AD (LOAD), is the most common form of Alzheimer's disease, representing about >95..
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Gilbert C FAURE
August 7, 2017 3:45 AM
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A blog on multiple sclerosis research
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Gilbert C FAURE
August 6, 2017 11:23 AM
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The absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus). The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34-56 from human myelin oligodendrocyte glycoprotein (MOG) formulated with a mineral oil (incomplete Freund’s adjuvant; IFA). Pathological aspects include demyelination of cortical grey matter with microglia activation, oxidative stress and redistribution of iron. When the peptide is formulated in complete Freund’s adjuvant (CFA), which contains mycobacteria that relay strong activation signals to myeloid cells, oxidative damage pathways are strongly boosted leading to more intensive pathology. The proven absence of immune potentiating danger signals in the MOG34-56/IFA formulation implies that a narrow population of antigen-experienced T cells present in the monkey’s immune repertoire is activated. This novel pathway involves the interplay of lymphocryptovirus (LCV)-infected B cells with MHC class Ib/Caja-E restricted CD8+CD56+ cytotoxic T lymphocytes.
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Gilbert C FAURE
July 31, 2017 7:36 AM
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A blog on multiple sclerosis research
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Gilbert C FAURE
July 24, 2017 1:20 PM
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Neuroscientists are torn over whether inflammation—a natural immune response—is causing a vast number of brain diseases.
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Gilbert C FAURE
July 17, 2017 3:08 AM
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Brussels, Belgium 6 July 2017 On 22 June, the EBC research project on the Value of Treatment of Brain Disorders (VoT) in Europe came to a close with the launch of a policy white paper includ…
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Gilbert C FAURE
July 10, 2017 2:10 PM
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In a rat model of hydrocephalus triggered by intraventricular hemorrhage, Kristopher Kahle and colleagues show that TLR4-NF-[kappa]B-dependent inflammatory signaling in the choroid plexus causes hypersecretion of cerebrospinal fluid that drives hydrocephalus. Targeting TLR4-NF-[kappa]B-mediated signaling or the NKCC1-SPAK complex ameliorates hydrocephalus.
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Gilbert C FAURE
June 29, 2017 12:15 PM
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Douvaras and colleagues generated microglia from pluripotent stem cells using a chemically
defined protocol through a myeloid progenitor. iPSC-derived microglia showed highly
motile processes, were able to phagocytose and responded to ADP with calcium transients.
Microglial identity was further confirmed by gene expression analysis comparing multiple
iPSC-derived microglia samples with primary microglia and peripheral blood or other
tissue-specific macrophages.
Via Krishan Maggon
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