Journal of Neuroimmunology RSS feed: Articles in Press. The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication. Works pertaining to multiple sclerosis, AIDS, amyotrophic lateral sclerosis, Guillain Barré Syndrome, myasthenia gravis, and brain tumors form a major focus. The scope of the Journal is broad, covering both research and clinical problems of neuroscientific interest. A major aim of the Journal is to encourage the development of immunologic approaches to analyse in further depth the interactions and specific properties of nervous tissue elements during development and disease. http://www.jni-journal.com//inpress?rss=yesElsevier Inc.en © 2012 Elsevier B.V. All rights reserved. Journal of Neuroimmunology0165-57282012-05-18 © 2012 Elsevier B.V. All rights reserved. healthpermissions@elsevier.comhttp://www.jni-journal.com/article/PIIS0165572812001294/abstract?rss=yesAbstract: A perturbed immunoregulation may be part of the pathogenesis of relapsing–remitting multiple sclerosis (RRMS). In this study, we demonstrate a dichotomy within the frequency of Treg among newly diagnosed RRMS patients but not in healthy controls. A group of RRMS patients was characterized by a significantly lower percentage of Treg cells than that of their matched, healthy controls, and this was inversely correlated with their score on the expanded disability status scale (EDSS). Since the EDSS reflected severity of the last attack, this study demonstrates a correlation between low frequency of Treg and severity of clinical disease in RRMS.Altered frequency of T regulatory cells is associated with disability status in relapsing–remitting multiple sclerosis patients - Corrected ProofLasse Bjerg, Anne Brosbøl-Ravnborg, Caroline Tørring, Anders Dige, Bettina Bundgaard, Thor Petersen, Per Höllsberg10.1016/j.jneuroim.2012.04.012Journal of Neuroimmunology (2012)2012-05-18Journal of Neuroimmunology2012-05-18http://www.jni-journal.com/article/PIIS0165572812001300/abstract?rss=yesAbstract: Effects of treatment of multiple sclerosis patients with IFN-β on elements of the antiviral immune response to herpesviruses were analysed in a longitudinal study. We found significantly increased seroreactivity to EBV EBNA-1, and to VZV, in patients who did not respond to IFN-β therapy. We found no significant changes in seroreactivity to EBV EA, or to HSV. For the same patient cohort, we have previously demonstrated significant decreases in seroreactivities to envelope antigens for the two human endogenous retroviruses HERV-H and HERV-W, closely linked to efficacy of therapy.We further searched for correlations between seroreactivities to EBV, HSV, and VZV, and levels of mannan-binding lectin (MBL), and MBL-associated serine protease 3. We found no such correlations.Our results are in accord with recent reports of increased seroreactivity to EBV EBNA-1, and to VZV in active MS, and they support that the herpesviruses EBV and VZV together with HERV-H/HERV-W and the antiviral immune response may play a role in MS development.Effects of interferon-beta therapy on elements in the antiviral immune response towards the human herpesviruses EBV, HSV, and VZV, and to the human endogenous retroviruses HERV-H and HERV-W in multiple sclerosis - Corrected ProofThor Petersen, Anné Møller-Larsen, Svend Ellermann-Eriksen, Steffen Thiel, Tove Christensen10.1016/j.jneuroim.2012.04.013Journal of Neuroimmunology (2012)2012-05-18Journal of Neuroimmunology2012-05-18SHORT COMMUNICATIONhttp://www.jni-journal.com/article/PIIS0165572812001208/abstract?rss=yesAbstract: Objective: Peripheral blood cells and inflammatory mediators have a detrimental effect on brain during cerebral ischemia. We investigated the immunologic changes on peripheral blood in the acute phase of ischemic stroke using RNA microarray.Methods: mRNA microarray and real time-polymerase chain reaction (RT-PCR) for genes of interest in microarray data were analyzed in 12 stroke patients and 12 controls. Plasma matrix metalloproteinase-9 (MMP-9) concentrations were measured in 120 stroke patients and 82 controls.Results: In microarray analysis, a total of 11 genes of interest showed different expression in patients with ischemic stroke. The three most highly expressed genes were C19orf59 (chromosome 19 open reading frame 59), MMP9 and IL18RAP (interleukin-18 receptor accessory protein), whereas gene with the lowest expression was GNLY (granulysin). The expression patterns of three selected genes (MMP9, IL18RAP and GNLY) were validated by RT-PCR. The plasma concentration of MMP-9 was significantly elevated in the stroke patients, and showed a weakly positive correlation with infarct volume. Gene set enrichment analysis (GSEA) showed that gene sets related to immunity and defense, signal transduction, transport and cell adhesion were significant in acute ischemic stroke.Conclusions: In the peripheral blood, numerous genes of inflammatory mediators, including MMP9, IL18RAP and GNLY, are altered in the acute phase of ischemic stroke. This stroke-specific gene expression profiling provides valuable information about the role of peripheral inflammation to the pathophysiological mechanism of ischemic stroke.Alteration of immunologic responses on peripheral blood in the acute phase of ischemic stroke: Blood genomic profiling study - Corrected ProofSeung-Hun Oh, Ok-Joon Kim, Dong-Ah Shin, Jihwan Song, Hanna Yoo, Yu-Kyung Kim, Jin-Kyeoung Kim10.1016/j.jneuroim.2012.04.005Journal of Neuroimmunology (2012)2012-05-16Journal of Neuroimmunology2012-05-16http://www.jni-journal.com/article/PIIS0165572812001270/abstract?rss=yesAbstract: Reduced protective immunity leads to viral persistence and demyelination in Theiler's murine encephalomyelitis. The aim of the present study was to compare the phenotype of brain-infiltrating leukocytes and cytokine expression in susceptible SJL and resistant C57BL/6 mice during Theilervirus-induced acute polioencephalitis. In contrast to C57/BL6 mice, SJL mice show an increased number of Foxp3+ regulatory T cells and CD45R+ B cells associated with delayed viral elimination and elevated IL-10 mRNA transcripts in the brain. Results substantiate the hypothesis that an imbalanced cytokine milieu during the early infection phase contributes to ineffective antiviral immunity in animals with a susceptible genetic background.Interleukin-10 expression during the acute phase is a putative prerequisite for delayed viral elimination in a murine model for multiple sclerosis - Corrected ProofVanessa Herder, Ingo Gerhauser, Stephanie Kristin Klein, Pedro Almeida, Maren Kummerfeld, Reiner Ulrich, Frauke Seehusen, Karl Rohn, Dirk Schaudien, Wolfgang Baumgärtner, Jochen Huehn, Andreas Beineke10.1016/j.jneuroim.2012.04.010Journal of Neuroimmunology (2012)2012-05-16Journal of Neuroimmunology2012-05-16http://www.jni-journal.com/article/PIIS0165572812000033/abstract?rss=yesAbstract: Multiple sclerosis (MS) is an autoimmune disease that targets the central nervous system (CNS). MS initially follows a relapsing–remitting course (RRMS) in which acute attacks are followed by a complete recovery. Eventually, 65% of the RRMS patients go on to develop secondary progressive MS (SPMS), characterized by the progressive and irreversible accumulation of neurological disability. It has been proposed that the transition from RRMS to SPMS results from changes in the nature of the inflammatory response and the progressive accumulation of neurodegeneration. To date, however, there is no reliable method to monitor the activity of the different immune and neurodegenerative processes that contribute to MS pathology. Thus, there is a need for biomarkers useful for the diagnosis, treatment and monitoring of MS patients. In this review, we discuss the potential use of lipids and the immune response against them as biomarkers of inflammation and neurodegeneration for MS.Lipids and lipid-reactive antibodies as biomarkers for multiple sclerosis - Corrected ProofFrancisco J. Quintana, Ada Yeste, Howard L. Weiner, Ruxandra Covacu10.1016/j.jneuroim.2012.01.002Journal of Neuroimmunology (2012)2012-05-14Journal of Neuroimmunology2012-05-14REVIEW ARTICLEhttp://www.jni-journal.com/article/PIIS016557281200121X/abstract?rss=yesAbstract: A B-cell activating factor of the tumor necrosis factor (TNF) family (BAFF) plays a crucial role in B-cell survival and maturation. An elevated serum BAFF level has been linked to several autoimmune diseases such as Sjögren syndrome, systemic lupus erythematosus and rheumatoid arthritis. Dermatomyositis (DM), one of autoimmune inflammatory myopathies, is characterized by inflammatory cell infiltration (CD4+ T cells and B cells) in skeletal muscle. Serum BAFF level was significantly high in DM, but the role of BAFF is not well understood. We investigated the role of BAFF in the immunopathogenesis of DM. To examine the transcriptional increase of BAFF gene expression, we performed RT-PCR analysis with skeletal muscle tissue that contained 4 controls and 9 patients with DM. Next, in order to detect BAFF expression and cellular localization in DM, we executed immunostaining in cryosection of biopsied muscle tissue with 4 controls and 8 patients and we adopted to double immunostaining to find which inflammatory cells expressed BAFF-receptor (BAFF-R). BAFF mRNA level was increased in DM patients compared with normal controls. BAFF expression was markedly increased at muscle fibers in the perifascicular area but not blood vessels. BAFF-R was expressed in inflammatory cells in skeletal muscle tissues of DM patients. We found that BAFF expression in muscle tissue may be associated with an increased number of CD4+ T cells and CD19+ B cells in DM. Our study results suggest that BAFF might play an important role in the pathogenesis of DM.The expression of BAFF in the muscles of patients with dermatomyositis - Corrected ProofAhmi Baek, Hyung Jun Park, Sang-Jun Na, Dong Suk Shim, Joon-Shik Moon, Young Yang, Young-Chul Choi10.1016/j.jneuroim.2012.04.006Journal of Neuroimmunology (2012)2012-05-10Journal of Neuroimmunology2012-05-10SHORT COMMUNICATIONhttp://www.jni-journal.com/article/PIIS0165572812001191/abstract?rss=yesAbstract: In this study we investigated the anti-inflammatory effects of chronic ethanol (EtOH) treatment on lipopolysaccharide (LPS)-stimulated C6 glioma cells. The cells were chronically treated with 200mM EtOH; coincubation with LPS and EtOH was obtained upon addition of 2μg/ml LPS to the incubation medium in the last 24h of EtOH exposure. We found that EtOH prevented the LPS-induced production of tumor necrosis factor α (TNFα) without decreasing cell viability. Either LPS treated or EtOH plus LPS treated cells presented upregulated glial fibrillary acidic protein (GFAP) and downregulated vimentin levels characterizing a program of reactive astrogliosis. Also, EtOH plus LPS stimulation greatly increased the oxidative stress generation evaluated by DCF-DA measurement, while either EtOH alone or LPS alone was unable to induce oxidative stress. Western blot analysis indicated that either EtOH, LPS or EtOH plus LPS treatments are unable to affect Akt/GSK3β signaling pathway. However, LPS alone and EtOH plus LPS co-treatment inhibited Erk phosphorylation. A dramatic loss of stress fibers was found in EtOH exposed cells, evaluated by cytochemistry using phalloidin-fluorescein. However, LPS alone was not able to disrupt actin organization. Furthermore, cells co-incubated with LPS and EtOH presented reversion of the disrupted stress fibers provoked by EtOH. Supporting this action, RhoA and vinculin immunocontent were upregulated in response to EtOH plus LPS. Interestingly, EtOH suppresses the inflammatory cascade (TNFα production) in response to LPS. Concomitantly it sustains Erk inhibition, increases oxidative stress generation and induces reactive astrogliosis in the presence of LPS, conditions associated with neurotoxicity. The effects observed were not supported by actin reorganization. Altogether, these findings suggest that Erk signaling inhibition could play a role in both suppressing TNFα production and inducing oxidative stress generation and astrogliosis, therefore modulating a dual action of EtOH plus LPS in glial cells.Dual action of chronic ethanol treatment on LPS-induced response in C6 glioma cells - Corrected ProofSamanta Oliveira Loureiro, Luana Heimfarth, Bárbara Ortiz de Lima, Marina C. Leite, Maria Cristina Guerra, Carlos Alberto Gonçalves, Regina Pessoa-Pureur10.1016/j.jneuroim.2012.04.004Journal of Neuroimmunology (2012)2012-05-07Journal of Neuroimmunology2012-05-07http://www.jni-journal.com/article/PIIS0165572812001221/abstract?rss=yesAbstract: The frequency of myositis-associated and myositis-specific autoantibodies (AAb) was compared in 51 s-IBM patients and a population control group. Non-organ specific AAb (ANA, anti-Ro52, anti-Ro60, anti-La, anti-RNP) but not anti-thyroid peroxidase, anti-tissue transglutaminase or myositis-specific antibodies, were more frequent in s-IBM patients, and 14/51 (27%) had another autoimmune disease (Sjögren's syndrome, thyroiditis, psoriasis, vitiligo). The presence of AAb did not correlate with carriage of HLA-DRB1*0301, but there was a negative correlation between ANA/anti-Ro52 and carriage of HLA-DRB1*1301. The findings in this cohort confirm that patients with sIBM do not show evidence of a muscle-specific humoral immune process but have an increased frequency of non-organ specific AAb and other autoimmune disorders.Frequency of autoantibodies and correlation with HLA-DRB1 genotype in sporadic inclusion body myositis (s-IBM): A population control study - Corrected ProofArada Rojana-udomsart, Christine Bundell, Ian James, Alison Castley, Patricia Martinez, Frank Christiansen, Peter Hollingsworth, Frank Mastaglia10.1016/j.jneuroim.2012.04.007Journal of Neuroimmunology (2012)2012-05-04Journal of Neuroimmunology2012-05-04http://www.jni-journal.com/article/PIIS0165572812000070/abstract?rss=yesAbstract: A substantial need exists for developing and validating a range of biomarkers that would address a number of important unmet clinical needs in the MS field. In spite of considerable efforts over last years, very few putative biomarkers have been fully validated or successfully integrated into routine clinical practice. Here, we consider some of the main challenges that have limited such effective translation from biomarker discovery to the bedside in the context of MS, the prototypic chronic human CNS inflammatory illness. We will define the types of biomarkers that would be relevant for MS, identify their ideal attributes, and then discuss individual challenges and strategies to overcome them.From bench to MS bedside: Challenges translating biomarker discovery to clinical practice - Corrected ProofSathyanath Rajasekharan, Amit Bar-Or, on behalf of the CIHR/MSSC NET in Clinical Autoimmunity10.1016/j.jneuroim.2012.01.006Journal of Neuroimmunology (2012)2012-03-02Journal of Neuroimmunology2012-03-02REVIEW ARTICLEhttp://www.jni-journal.com/article/PIIS0165572812000100/abstract?rss=yesAbstract: Metabolomic analysis has the potential to generate disease-specific metabolite signatures unique to individuals. Autoimmune illnesses, such as inflammatory uveitis, have highlighted the discriminative power of metabolomics by allowing disease sub-classification. Elucidating surrogate markers for neurological disease is particularly important, given the constraints in accessing central nervous system tissue in vivo. Metabolomic analysis, using either 1H NMR spectroscopy or mass spectroscopy can be performed using biofluids such as urine, blood or cerebrospinal fluid and may permit the identification of disease specific metabolite signatures which may be useful as disease biomarkers. This is particularly relevant to complex diseases such as multiple sclerosis where promising preliminary work has been carried out. Future work in this field may well generate metabolite profiles to monitor disease evolution, prognosticate and guide therapeutic decisions.The role of metabolomics in neurological disease - Corrected ProofGhaniah Hassan-Smith, Graham R. Wallace, Michael R. Douglas, Alexandra J. Sinclair10.1016/j.jneuroim.2012.01.009Journal of Neuroimmunology (2012)2012-02-17Journal of Neuroimmunology2012-02-17REVIEW ARTICLEhttp://www.jni-journal.com/article/PIIS016557281100364X/abstract?rss=yesAbstract: The field of epigenomics involves the study of chromatin, the three dimensional complex of DNA, protein and non-coding RNAs that determines the accessibility of DNA by the transcriptional machinery. The epigenome varies from cell to cell and reflects the effect of external stimuli on cell fate and cell state. Thanks to emerging platforms and analysis methods, the systematic characterization of chromatin conformation throughout the genome has begun and has yielded several reference epigenome maps for a growing number of cell types. Such maps are enabling insights into the correlation architecture of different epigenomic marks: a number of discrete chromatin states are found across different cell types. The combination of these reference maps and robust platforms for genome-wide data generation has introduced a new era in which studies of human disease are becoming feasible. Little is known about the role of the epigenome in MS, but it is likely that, as in other inflammatory disease, susceptibility factors and events along the course of the disease will alter the chromatin state of different cell types in patients with MS. Here, we review different strategies for the characterization of the epigenome and how these strategies could be used to implement new studies to explore how alterations of chromatin architecture establish a dysregulated transcriptional state in the context of MS.Exploring the role of the epigenome in multiple sclerosis: A window onto cell-specific transcriptional potential - Corrected ProofAnna Kaliszewska, Philip L. De Jager10.1016/j.jneuroim.2011.12.012Journal of Neuroimmunology (2012)2012-02-02Journal of Neuroimmunology2012-02-02REVIEW ARTICLEhttp://www.jni-journal.com/article/PIIS0165572811003699/abstract?rss=yesAbstract: The advent of next generation sequencing technologies has opened new possibilities in the analysis of human disease. In this review we present the main next-generation sequencing technologies, with their major contributions and possible applications to the study of the genetic etiology of complex diseases.Next-generation sequencing approaches for genetic mapping of complex diseases - Corrected ProofFerran Casals, Youssef Idaghdour, Julie Hussin, Philip Awadalla10.1016/j.jneuroim.2011.12.017Journal of Neuroimmunology (2012)2012-01-30Journal of Neuroimmunology2012-01-30REVIEW ARTICLEhttp://www.jni-journal.com/article/PIIS0165572812000021/abstract?rss=yesAbstract: New “omic” technologies and their application to systems biology approaches offer new opportunities for biomarker discovery in complex disorders, including multiple sclerosis (MS). Recent studies using massive genotyping, DNA arrays, antibody arrays, proteomics, glycomics, and metabolomics from different tissues (blood, cerebrospinal fluid, brain) have identified many molecules associated with MS, defining both susceptibility and functional targets (e.g., biomarkers). Such discoveries involve many different levels in the complex organizational hierarchy of humans (DNA, RNA, protein, etc.), and integrating these datasets into a coherent model with regard to MS pathogenesis would be a significant step forward. Given the dynamic and heterogeneous nature of MS, validating biomarkers is mandatory. To develop accurate markers of disease prognosis or therapeutic response that are clinically useful, combining molecular, clinical, and imaging data is necessary. Such an integrative approach would pave the way towards better patient care and more effective clinical trials that test new therapies, thus bringing the paradigm of personalized medicine in MS one step closer.Data integration and systems biology approaches for biomarker discovery: Challenges and opportunities for multiple sclerosis - Corrected ProofPablo Villoslada, Sergio Baranzini10.1016/j.jneuroim.2012.01.001Journal of Neuroimmunology (2012)2012-01-27Journal of Neuroimmunology2012-01-27REVIEW ARTICLEhttp://www.jni-journal.com/article/PIIS0165572811003043/abstract?rss=yesAbstract: Multiple sclerosis is a disabling inflammatory and neurodegenerative disorder that predominantly affects young adults. There is a great need for biomarkers, which could elucidate pathology as well as provide prognosis of disease progression and therapy response in multiple sclerosis. Rapidly evolving, technology driven applications such as mass spectrometry based proteomics are currently being developed for this purpose. In this review, we will outline the current status of the field and detail a number of the bottlenecks as well as future prospects of this type of biomarker research.Proteomics technologies for biomarker discovery in multiple sclerosis - Corrected ProofVaibhav Singh, Rogier Q. Hintzen, Theo M. Luider, Marcel P. Stoop10.1016/j.jneuroim.2011.11.004Journal of Neuroimmunology (2011)2011-12-02Journal of Neuroimmunology2011-12-02REVIEW ARTICLEhttp://www.jni-journal.com/article/PIIS016557281100292X/abstract?rss=yesAbstract: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. miRNAs are highly expressed in cells of the immune and nervous system, attesting to their importance in Neuroimmunology. Besides their involvement in modulation of physiological and pathological processes, miRNAs hold high promise as disease biomarkers, therapeutic agents and/or drug targets. Several studies have recently explored the involvement of miRNAs in Multiple Sclerosis (MS) using a variety of miRNA profiling techniques. In this review, we discuss basic miRNA biology and nomenclature, the techniques available for miRNA profiling research and recent miRNA profiling studies in Multiple Sclerosis.miRNA profiling for biomarker discovery in multiple sclerosis: From microarray to deep sequencing - Corrected ProofMireia Guerau-de-Arellano, Hansjuerg Alder, Hatice Gulcin Ozer, Amy Lovett-Racke, Michael K. Racke10.1016/j.jneuroim.2011.10.006Journal of Neuroimmunology (2011)2011-11-11Journal of Neuroimmunology2011-11-11REVIEW ARTICLEhttp://www.jni-journal.com/article/PIIS0165572807001130/abstract?rss=yesChemokines and chemokine receptors in the nervous system - Corrected Proof10.1016/j.jneuroim.2007.03.017Journal of Neuroimmunology (2007)2007-05-11Journal of Neuroimmunology2007-05-11ANNOUNCEMENT