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Infection in multiple sclerosis

Jonatan Salzer, Rasmus Svenningsson, Peter Alping, Lenka Novakova, Anna Björck, Katharina Fink, Protik Islam-Jakobsson, Clas Malmeström, Markus Axelsson, Mattias Vågberg, Peter Sundström, Jan Lycke, Fredrik Piehl, Anders Svenningsson
OBJECTIVE: To investigate the safety and efficacy of rituximab in multiple sclerosis (MS). METHODS: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2-5 according to the Common Terminology Criteria for Adverse Events were recorded. RESULTS: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 primary progressive MS (PPMS)...
October 19, 2016: Neurology
Marisa P McGinley, Brandon P Moss, Jeffrey A Cohen
Monoclonal antibodies are a potent therapeutic approach for relapsing-remitting multiple sclerosis. This group of medications comprises diverse mechanisms of action resulting in both shared and unique adverse effects. Areas covered: The major trials and safety profiles of natalizumab, alemtuzumab, daclizumab, rituximab, and ocrelizumab are discussed. While each drug has a unique safety profile, one of the potential safety concerns for all of these drugs is infection, including for some progressive multifocal leukoencephalopathy...
October 19, 2016: Expert Opinion on Drug Safety
Katharina D Hauck, Shaolin Wang, Charles Vincent, Peter C Smith
BACKGROUND: There is little satisfactory evidence on the harm of safety incidents to patients, in terms of lost potential health and life-years. OBJECTIVE: To estimate the healthy life-years (HLYs) lost due to 6 incidents in English hospitals between the years 2005/2006 and 2009/2010, to compare burden across incidents, and estimate excess bed-days. RESEARCH DESIGN: The study used cross-sectional analysis of the medical records of all inpatients treated in 273 English hospitals...
October 6, 2016: Medical Care
Mathew Clement, James A Pearson, Stephanie Gras, Hugo A van den Berg, Anya Lissina, Sian Llewellyn-Lacey, Mark D Willis, Tamsin Dockree, James E McLaren, Julia Ekeruche-Makinde, Emma Gostick, Neil P Robertson, Jamie Rossjohn, Scott R Burrows, David A Price, F Susan Wong, Mark Peakman, Ania Skowera, Linda Wooldridge
CD8(+) T-cells play a role in the pathogenesis of autoimmune diseases such as multiple sclerosis and type 1 diabetes. However, drugs that target the entire CD8(+) T-cell population are not desirable because the associated lack of specificity can lead to unwanted consequences, most notably an enhanced susceptibility to infection. Here, we show that autoreactive CD8(+) T-cells are highly dependent on CD8 for ligand-induced activation via the T-cell receptor (TCR). In contrast, pathogen-specific CD8(+) T-cells are relatively CD8-independent...
October 17, 2016: Scientific Reports
Linda Cook
Over the last 10 years, the number of identified polyomaviruses has grown to more than 35 subtypes, including 13 in humans. The polyomaviruses have similar genetic makeup, including genes that encode viral capsid proteins VP1, 2, and 3 and large and small T region proteins. The T proteins play a role in viral replication and have been implicated in viral chromosomal integration and possible dysregulation of growth factor genes. In humans, the Merkel cell polyomavirus has been shown to be highly associated with integration and the development of Merkel cell cancers...
August 2016: Microbiology Spectrum
Matthew M Dooley, Samantha L de Gannes, Kristi A Fu, J William Lindsey
Multiple sclerosis (MS) is associated with Epstein-Barr virus (EBV) infection, and the antibody response to EBV is reported to be increased in MS. EBV contains multiple antigens, and only a few have been investigated. Our hypothesis is that MS patients will have an increased antibody response to only selected EBV antigens. We used immunoprecipitation and quantitative mass spectrometry to identify candidate EBV antigens. We then measured the antibody response to 10 individual EBV proteins with quantitative ELISA...
October 15, 2016: Journal of Neuroimmunology
Takuma Tsuzuki Wada, Kojiro Sato, Toshihide Mimura
We encountered a case of a middle-aged woman with systemic lupus erythematosus. As the patient had progressive peripheral neuropathy including foot drop, we intended to treat her with intensive immunosuppressive therapy as soon as possible. Pretreatment assessment, however, revealed multiple nodular lesions in the lungs and bones, suggesting disseminated tumor metastasis or miliary tuberculosis. To our surprise, gallium and bone scintigraphy as well as cytodiagnosis revealed no sign of malignancy or infection, leading us to suspect the presence of another multisystem disorder...
March 2016: Eur J Rheumatol
Carine Savarin, Cornelia C Bergmann, David R Hinton, Stephen A Stohlman
Viral infections have long been implicated as triggers of autoimmune diseases, including multiple sclerosis (MS), a central nervous system (CNS) inflammatory demyelinating disorder. Epitope spreading, molecular mimicry, cryptic antigen, and bystander activation have been implicated as mechanisms responsible for activating self-reactive (SR) immune cells, ultimately leading to organ-specific autoimmune disease. Taking advantage of coronavirus JHM strain of mouse hepatitis virus (JHMV)-induced demyelination, this study demonstrates that the host also mounts counteractive measures to specifically limit expansion of endogenous SR T cells...
2016: Frontiers in Immunology
Alessandra Bua, Melania Ruggeri, Stefania Zanetti, Paola Molicotti
Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by damage to myelin and axons, over time leading to progressive neuronal degeneration and microglial activation. There is still no curative treatment, but during the last 20 years eight different therapies have become available including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, fingolimod, alemtuzumab, mitoxantrone and teriflunomide. Teriflunomide is an immunomodulatory drug that exerts an inhibitory effect on T cell activation in central nervous system of the patients with multiple sclerosis...
October 4, 2016: Medical Microbiology and Immunology
Emanuele D'Amico, Aurora Zanghì, Carmela Leone, Hayrettin Tumani, Francesco Patti
Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system caused by the John Cunningham virus (JCV) that has been associated with therapeutic immunosuppression in patients with multiple sclerosis (MS). So far, more than 600 cases of PML have been reported in association with natalizumab administration. There have also been confirmed cases of PML in individuals who received fingolimod and dimethyl fumarate without previous natalizumab treatment. The new licensed disease-modifying therapies for MS carry the risk of immunosuppressant and so of JCV reactivation...
September 30, 2016: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Saskia M Leibowitz, Jun Yan
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways are involved in cell immune responses, apoptosis and infections. In multiple sclerosis (MS), NF-κB pathways are changed, leading to increased levels of NF-κB activation in cells. This may indicate a key role for NF-κB in MS pathogenesis. NF-κB signaling is complex, with many elements involved in its activation and regulation. Interestingly, current MS treatments are found to be directly or indirectly linked to NF-κB pathways and act to adjust the innate and adaptive immune system in patients...
2016: Frontiers in Molecular Neuroscience
Saeideh Najafi, Masood Ghane, Vahdat Poortahmasebi, Seyed Mohammad Jazayeri, Shahrokh Yousefzadeh-Chabok
BACKGROUND: Multiple sclerosis (MS) is a chronic debilitating disease known as one of the most common neurological dysfunctions in young adults. Recent studies suggest that infections with herpesviruses play a critical role in the pathogenesis of MS. OBJECTIVES: The present investigation aimed to detect the presence of cytomegalovirus (CMV) in patients with MS using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) methods. PATIENTS AND METHODS: Plasma and peripheral blood mononuclear cells (PBMCs) were collected from MS patients (n = 82) and from blood donors as control group (n = 89)...
July 2016: Jundishapur Journal of Microbiology
Stanley Cohan
Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit-risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56(bright) natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS...
2016: Biologics: Targets & Therapy
Amanda K Huber, David A Giles, Benjamin M Segal, David N Irani
Eotaxins are C-C motif chemokines first identified as potent eosinophil chemoattractants. They facilitate eosinophil recruitment to sites of inflammation in response to parasitic infections as well as allergic and autoimmune diseases such as asthma, atopic dermatitis, and inflammatory bowel disease. The eotaxin family currently includes three members: eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26). Despite having only ~30% sequence homology to one another, each was identified based on its ability to bind the chemokine receptor, CCR3...
September 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Navina L Chrobok, Claudia Sestito, Micha M M Wilhelmus, Benjamin Drukarch, Anne-Marie van Dam
Monocytes and macrophages are key players in inflammatory processes following an infection or tissue damage. Monocytes adhere and extravasate into the inflamed tissue, differentiate into macrophages, and produce inflammatory mediators to combat the pathogens. In addition, they take up dead cells and debris and, therefore, take part in the resolution of inflammation. The multifunctional enzyme tissue Transglutaminase (TG2, tTG) is known to participate in most of those monocyte- and macrophage-mediated processes...
September 22, 2016: Amino Acids
Elena Grebenciucova, Anthony T Reder, Jacqueline T Bernard
BACKGROUND: Fingolimod is a disease-modifying agent used in the treatment of relapsing/remitting multiple sclerosis. In MS clinical studies, the overall rate of infections in fingolimod group was overall similar to placebo, except for slightly more common lower respiratory tract infections and to a lesser extent HSV. Recently, an increasing number of cryptococcal infections associated with a long-term use of this medication have been reported. METHODS: We reviewed literature for cases of cryptococcal infection associated with the use of fingolimod and reported a case at our institution, as well as carefully evaluated the established immune mechanisms of the medication and discussed new insights into its short-term and long-term immunologic effects that may become important in the context of risk of infection...
September 2016: Multiple Sclerosis and related Disorders
Bassem I Yamout, Nuhad Abou Zeid, Ali J Taha, Maya M Zeineddine, Samia J Khoury
Natalizumab was the first FDA-approved monoclonal antibody for the treatment of multiple sclerosis (MS). We report on 3 natalizumab-treated patients who developed herpes zoster infections. In addition to progressive multifocal leukoencephelopathy, other opportunistic infections have been rarely reported during Natalizumab treatment. We believe that clinicians need heightened awareness of these infections in view of the risks of serious complications.
September 2016: Multiple Sclerosis and related Disorders
Melanie D Ward, David E Jones, Myla D Goldman
Fingolimod (Gilenya, Novartis) is an oral sphingosine-1-phosphate analogue used in the treatment of relapsing multiple sclerosis (MS). Fingolimod treatment is associated with relative lymphopenia and was associated with an increased risk of herpes infection in clinical trials. In the post-marketing setting, fingolimod has been associated with several cases of cryptococcal meningitis, recently prompting an update to its prescribing information. To date, all cases have been associated with active treatment with fingolimod...
September 2016: Multiple Sclerosis and related Disorders
D S Goodin
MS-pathogenesis involves both genetic-susceptibility and environmental determinants. Three (or more) sequential environmental-factors are implicated. The first acts near birth, the second acts during childhood/adolescence, and the third acts subsequently. Two candidate factors (vitamin D deficiency and Epstein-Barr viral infection) seem particularly well-suited to the first two environmental-events but other factors (e.g., obesity and smoking behavior) seem also to be involved in the causal scheme. MS-pathogenesis can be modeled by incorporating both the environmental and genetic-factors into a causal scheme, which can then help to explain some of the changes in MS-epidemiology (e...
2016: Handbook of Clinical Neurology
Etvi Juntunen, Teppo Salminen, Sheikh M Talha, Iida Martiskainen, Tero Soukka, Kim Pettersson, Matti Waris
Myxovirus resistance protein A (MxA) is a biomarker of interferon-induced gene expression state involved in many viral infections and some autoimmune disorders. It has a variety of potential utilities in clinical diagnostics, including distinguishing between bacterial and viral infections. Currently, MxA-assays are used for monitoring of IFN-β therapy in multiple sclerosis (MS) patients. As a proof-of-concept for rapid quantitative measurement of interferon response, a lateral flow immunoassay (LFIA) with upconverting nanoparticle (UCNP) reporters was developed and evaluated with clinical whole blood samples to assess the potential for a rapid and user-friendly quantitative assay for MxA, since the currently available rapid test for MxA (FebriDX) produces only qualitative result...
September 16, 2016: Journal of Medical Virology
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