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Find video protocols related to scientific articles indexed in Pubmed.
Validation of semaphorin 7A and ala-?-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis.
J Neuroinflammation
PUBLISHED: 09-15-2014
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In a previous proteomics study using pooled cerebrospinal fluid (CSF) samples, we proposed apolipoprotein AI, apolipoprotein AIV, vitronectin, plasminogen, semaphorin 7A, and ala-?-his-dipeptidase as candidate biomarkers associated with the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndromes (CIS). Here, we aimed to validate these results in individual CSF samples using alternative techniques.
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Validation of semaphorin 7A and ala-ß-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis.
J Neuroinflammation
PUBLISHED: 09-15-2014
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BackgroundIn a previous proteomics study using pooled cerebrospinal fluid (CSF) samples, we proposed apolipoprotein AI, apolipoprotein AIV, vitronectin, plasminogen, semaphorin 7A, and ala-ß-his-dipeptidase as candidate biomarkers associated with the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndromes (CIS). Here, we aimed to validate these results in individual CSF samples using alternative techniques.MethodsIn a first replication study, levels of apolipoproteins AI and AIV, vitronectin, and plasminogen were measured by ELISA in CSF and serum of 56 CIS patients (29 patients who converted to CDMS (MS converters) and 27 patients who remained with CIS during follow-up (MS non-converters)) and 26 controls with other neurological disorders. Semaphorin 7A and ala-ß-his-dipeptidase levels were determined by selected reaction monitoring (SRM) in CSF of 36 patients (18 MS converters, 18 non-converters) and 20 controls. In a second replication study, apolipoprotein AI levels were measured by ELISA in CSF of 74 CIS patients (47 MS converters, 27 non-converters) and 50 individual controls, and levels of semaphorin 7A and ala-beta-his-dipeptidase were determined by SRM in 49 patients (24 MS converters, 25 non-converters) and 22 controls.ResultsCSF levels of apolipoprotein AI were increased (P =0.043) and levels of semaphorin 7A and ala-ß-his-dipeptidase decreased (P =4.4¿×¿10¿10 and P =0.033 respectively) in MS converters compared to non-converters. No significant differences were found in serum levels for apolipoproteins AI and AIV, vitronectin, and plasminogen. Findings with semaphorin 7A and ala-ß-his-dipeptidase were also validated in the second replication study, and CSF levels for these two proteins were again decreased in MS converters versus non-converters (P =1.2¿×¿10¿4 for semaphorin 7A; P =3.7¿×¿10¿8 for ala-ß-his-dipeptidase). Conversely, apolipoprotein AI findings were not replicated and CSF levels for this protein did not significantly differ between groups. Furthermore, CSF semaphorin 7A levels were negatively associated with the number of T2 lesions at baseline and one-year follow-up.ConclusionsThese results validate previous findings for semaphorin 7A and ala-ß-his-dipeptidase, and suggest that these proteins play a role as CSF biomarkers associated with the conversion to CDMS in CIS patients.
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Guidelines for uniform reporting of body fluid biomarker studies in neurologic disorders.
Neurology
PUBLISHED: 08-22-2014
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The aim of these guidelines is to make the process of reporting body fluid biomarker studies in neurologic disorders more uniform and transparent, in line with existing standards for reporting research in other biomedical areas. Although biomarkers have been around for decades, there are concerns over the high attrition rate of promising candidate biomarkers at later phases of development.
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Circulating microparticles reflect treatment effects and clinical status in multiple sclerosis.
Biomark Med
PUBLISHED: 08-16-2014
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To evaluate whether circulating microparticles (MPs) derived from three cell subtypes (platelets, total leukocytes or monocytes) obtained from multiple sclerosis (MS) patients were modulated depending on the clinical status and to investigate the effect of treatments on MP levels.
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Sperm-associated antigen 16 is a novel target of the humoral autoimmune response in multiple sclerosis.
J. Immunol.
PUBLISHED: 08-01-2014
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We have previously identified eight novel autoantibody targets in the cerebrospinal fluid of multiple sclerosis (MS) patients, including sperm-associated Ag 16 (SPAG16). In the current study, we further investigated the autoantibody response against SPAG16-a protein with unknown function in the CNS-and its expression in MS pathology. Using isoelectric focusing, we detected SPAG16-specific oligoclonal bands in the cerebrospinal fluid of 5 of 23 MS patients (22%). Analysis of the anti-SPAG16 Ab reactivity in the plasma of a total of 531 donors using ELISA demonstrated significantly elevated anti-SPAG16 Ab levels (p = 0.002) in 32 of 153 MS patients (21%) compared with all other control groups with 95% specificity for the disease. To investigate the pathologic relevance of anti-SPAG16 Abs in vivo, anti-SPAG16 Abs were injected in mice with experimental autoimmune encephalomyelitis, resulting in a significant disease exacerbation. Finally, we demonstrated a consistent upregulation of SPAG16 in MS brain and experimental autoimmune encephalomyelitis spinal cord lesions, more specifically in reactive astrocytes. We conclude that SPAG16 is a novel autoantibody target in a subgroup of MS patients and in combination with other diagnostic criteria, elevated levels of anti-SPAG16 Abs could be used as a biomarker for diagnosis. Furthermore, the pathologic relevance of anti-SPAG16 Abs was shown in vivo.
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Intrathecal somatic hypermutation of IgM in multiple sclerosis and neuroinflammation.
Brain
PUBLISHED: 07-23-2014
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Intrathecal oligoclonal bands of the cerebrospinal fluid are considered the most important immunological biomarkers of multiple sclerosis. They typically consist of clonally expanded IgG antibodies that underwent affinity maturation during sustained stimulation by largely unknown antigens. In addition, ?40% of patients with multiple sclerosis have oligoclonal bands that consist of expanded IgM antibodies. We investigated the molecular composition of IgM- and IgG-chains from cerebrospinal fluid of 12 patients with multiple sclerosis, seven patients with other neurological diseases, and eight healthy control subjects by high-throughput deep-sequencing and single-cell PCR. Further, we studied the expression of activation-induced cytidine deaminase, the key enzyme for affinity maturation of antibodies, in cerebrospinal fluid samples of 16 patients. From the cerebrospinal fluid of two multiple sclerosis patients we isolated single B cells and investigated the co-expression of antibody chains with activation-induced cytidine deaminase. In striking contrast to IgM-chains from peripheral blood, IgM-chains from cerebrospinal fluid of patients with multiple sclerosis or neuroborreliosis showed a high degree of somatic hypermutation. We found a high content of mutations that caused amino acid exchanges as compared to silent mutations. In addition, more mutations were found in the complementarity determining regions of the IgM-chains, which interact with yet unknown antigens, as compared to framework regions. Both observations provide evidence for antigen-driven affinity maturation. Furthermore, single B cells from the cerebrospinal fluid of patients with multiple sclerosis co-expressed somatically hypermutated IgM-chains and activation-induced cytidine deaminase, an enzyme that is crucial for somatic hypermutation and class switch recombination of antibodies and is normally expressed during activation of B cells in germinal centres. Clonal tracking of particular IgM(+) B cells allowed us to relate unmutated ancestor clones in blood to hypermutated offspring clones in CSF. Unexpectedly, however, we found no evidence for intrathecal isotype switching from IgM to IgG. Our data suggest that the intrathecal milieu sustains a germinal centre-like reaction with clonal expansion and extensive accumulation of somatic hypermutation in IgM-producing B cells.
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Opsoclonus-myoclonus syndrome and limbic encephalitis associated with GABAB receptor antibodies in CSF.
J. Neuroimmunol.
PUBLISHED: 03-24-2014
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We report a case of a woman who had two consecutive autoimmune neurological disorders, including an opsoclonus-myoclonus syndrome (OMS) and limbic encephalitis (LE), with positive titers of GABAB receptor antibodies. The patient never developed seizures or had an underlying tumor after 4 years of follow-up.
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Regulatory lymphocytes are key factors in MHC-independent resistance to EAE.
J Immunol Res
PUBLISHED: 03-12-2014
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Resistant and susceptible mouse strains to experimental autoimmune encephalomyelitis (EAE), an inducible demyelinating experimental disease serving as animal model for multiple sclerosis, have been described. We aimed to explore MHC-independent mechanisms inducing resistance to EAE.
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Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III).
Rev Neurol
PUBLISHED: 09-21-2013
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The most significant data presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in France in October 2012, have been summarised in the fifth edition of the Post-ECTRIMS Experts Meeting, held in Madrid in October 2012. This led to the drafting of this review, which has been published in three parts. This third part of the Post-ECTRIMS review presents the findings from the latest studies conducted with disease-modifying treatments, more specifically with glatiramer acetate, laquinimod, ponesimod, BG-12, teriflunomide, daclizumab, natalizumab and secukinumab (AIN457). Likewise, we also address the reasons that justify the search for innovative treatments for multiple sclerosis, with antigen-specific therapy, cell therapy and therapy aimed at promoting remyelination being highlighted among other future therapeutic strategies. Access to new pharmacological agents and the complexity of the therapy of multiple sclerosis in the future will require new design strategies and directions in clinical trials, including the use of surrogate markers, new statistical applications, superiority, inferiority or equivalence clinical trials and adaptable designs.
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Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).
Rev Neurol
PUBLISHED: 08-27-2013
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The most relevant data presented at the 28th edition of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2012 in France, have been summarized in the fifth edition of the Post-ECTRIMS Expert Meeting held in Madrid in October 2012. The present review summarizes the views and results of the meeting and is being published in three parts. This first part of the Post-ECTRIMS review addresses the incidence and prevalence of multiple sclerosis (MS), which has increased at the global level, largely due to the increased incidence in women because the risk of developing the disease is increased in females, with minimal concurrent effect on the progression of MS. Sexual dimorphism is evident in MS, and all evidence points to an interaction between hormonal, genetic, and environmental factors. The paediatric population represents an ideal group to study susceptibility factors to the disease, which is why collaborative studies designed to increase the patient samples are being considered, given its low prevalence. In this review, inflammatory and neurodegenerative phenomena involved in the pathogenesis of the disease and that have a cause-and-effect or shared relationship with the disease are being discussed. Current hypotheses suggest a phenomenon of compartmentalization, presumably inaccessible to current immunomodulatory therapy. Among the possible mechanisms involved in these processes of inflammation and demyelination, the role of Th17 cells, mitochondrial dysfunction, early disruption of astrocytic processes, and chronic hypoxia are discussed.
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Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis.
Mult. Scler.
PUBLISHED: 05-21-2013
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The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus definitions and nomenclature for the following groups: healthy controls (HCs), spinal anesthesia subjects (SASs), inflammatory neurological disease controls (INDCs), peripheral inflammatory neurological disease controls (PINDCs), non-inflammatory neurological controls (NINDCs), symptomatic controls (SCs). Furthermore, we discuss the application of these control groups in specific study designs, such as for diagnostic biomarker studies, prognostic biomarker studies and therapeutic response studies. Application of these uniform definitions will lead to better comparability of biomarker studies and optimal use of available resources. This will lead to improved quality of CSF biomarker research in MS and related disorders.
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[Biomarkers in multiple sclerosis].
Rev Neurol
PUBLISHED: 03-23-2013
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Multiple sclerosis is the most frequent disabling neurological disease in young adults. Its development includes independent processes of inflammation, demyelination, neurodegeneration, gliosis and repair, which are responsible for the heterogeneity and individual variability in the expression of the disease, its prognosis and response to treatment. As part of personalised medicine, the progress made in the search for new biomarkers has identified promising candidates that may be useful for the early diagnosis of the disease, for detecting prognostic and developmental profiles of the disease, and for monitoring the response to treatment. Unfortunately, few of them have been validated adequately, which prevents them from being applied in clinical practice. In view of the latest findings, the experts recommend orienting research in another direction, not so much towards the discovery of new molecules or imaging techniques, but instead towards a clinical validation of these markers, with the aim of fostering translational research. This review offers an update on the information about the biomarkers in multiple sclerosis that have currently been validated and are thus potential candidates, as well as looking at their value in the diagnosis, prognosis, evaluation of the development of the disability caused by the disease and the response to therapy.
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Autoantigen induced clonal expansion in immortalized B cells from the peripheral blood of multiple sclerosis patients.
J. Neuroimmunol.
PUBLISHED: 03-05-2013
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We studied Ig heavy chain (VDJ) sequences and antigen reactivity of 412 immortalized B cell lines from the peripheral blood of 10 multiple sclerosis (MS) patients, 4 clinically isolated syndrome (CIS) patients and 6 healthy controls (HCs). 78/238 (32.8%) MS and CIS B cell lines were part of 9 clonally expanded B cell populations, of which 5 were present in multiple patients. Increased VH1 gene family usage was evidenced for MS B cells, with 29.2% expressing VH1-69. Affinity maturation in MS and CIS was indicated by increased Ig VDJ mutations. Autoantibody producing B cells reactive to intracellular antigens were significantly higher in MS (25%) and CIS (28%) patients than in HCs (5%), including 3/9 expanded B cell clones. Specificity for phosphatidylcholine was observed for 1/9 B cell clones. These findings indicate clonally expanded autoreactive B cells with affinity maturation in the peripheral blood in MS and CIS.
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High frequency of co-infection by Epstein-Barr virus types 1 and 2 in patients with multiple sclerosis.
Mult. Scler.
PUBLISHED: 07-14-2011
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The existence of Epstein-Barr virus (EBV) strains specifically associated with multiple sclerosis (MS) is a matter of controversy. Little is also known about the prevalence of EBV types 1 and 2 in MS patients and the presence of co-infections by both strains.
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Increased peripheral blood CD5+ B cells predict earlier conversion to MS in high-risk clinically isolated syndromes.
Mult. Scler.
PUBLISHED: 03-24-2011
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Clinically isolated syndrome patients (CIS) with oligoclonal IgG bands (OCGB) are at high risk for clinically definite multiple sclerosis (MS). However, the outcome for individual patients is unpredictable and the search for reliable blood markers predicting early conversion to multiple sclerosis (MS) has clinical relevance. CD5+ B cells (CD5+Bc) are involved in some autoimmune diseases. This study investigated whether high blood CD5+Bc percentage can predict CIS conversion to MS. Fifty-five consecutive CIS showing OCGB were prospectively studied. Every patient underwent a brain MRI study and a flow cytometry analysis of CD5+Bc percentage. Conversion to MS was studied during follow-up. The CD5+Bc percentage was assessed in 40 controls and a cut-off value of 3.5% (mean+2 SD) was calculated. A blood CD5+Bc percentage above this value predicted earlier conversion to MS in the whole group (hazard ratio [HR]: 3.40; 95% confidence interval [CI]: 1.69-6.68; p=0.0005) and in CIS patients fulfilling three or more Barkhof-Tintoré criteria plus OCGB, who showed higher risk for MS (HR: 3.79; 95% CI: 1.86-15.32; p=0.0018). Multivariate analysis also showed a predictive value for high blood CD5+Bc count (HR: 4.3; 95% CI: 1.9-9.5; p<0.0001). It was concluded that high percentages of CD5+Bc independently associate with increased risk of early conversion to MS in CIS patients with OCGB and Barkhof-Tintoré criteria.
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Brain atrophy and lesion load are related to CSF lipid-specific IgM oligoclonal bands in clinically isolated syndromes.
Neuroradiology
PUBLISHED: 01-27-2011
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The objective of this work is to study the relationship between the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in CSF, with both T2 lesion volume (T2LV) accumulation and brain atrophy (percentage change of brain volume-PCBV-and brain parenchyma fraction-BPF) in patients with clinically isolated syndromes (CIS) suggestive of demyelination.
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Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis.
Brain
PUBLISHED: 03-17-2010
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In most patients with multiple sclerosis, the disease initiates with a first attack or clinically isolated syndrome. At this phase, magnetic resonance imaging is an important predictor of conversion to multiple sclerosis. With the exception of oligoclonal bands, the role of other biomarkers in patients with clinically isolated syndrome is controversial. In the present study, we aimed to identify proteins associated with conversion to multiple sclerosis in patients with clinically isolated syndrome. We applied a mass spectrometry-based proteomic approach (isobaric labelling) to previously collected pooled cerebrospinal fluid samples from patients with clinically isolated syndrome, who subsequently converted to clinically definite multiple sclerosis (n=30) and patients who remained as having clinically isolated syndrome (n=30). Next, three of the most represented differentially expressed proteins, i.e. ceruloplasmin, vitamin D-binding protein and chitinase 3-like 1 were selected for validation in individual cerebrospinal fluid samples by enzyme-linked immunosorbent assay. Only chitinase 3-like 1 was validated and cerebrospinal fluid levels were increased in patients who converted to clinically definite multiple sclerosis compared with patients who continued as clinically isolated syndrome (P=0.00002) and controls (P=0.012). High cerebrospinal fluid levels of chitinase 3-like 1 significantly correlated with the number of gadolinium enhancing lesions and the number of T2 lesions observed in brain magnetic resonance imaging scans performed at baseline, and were associated with disability progression during follow-up and shorter time to clinically definite multiple sclerosis (log-rank P-value=0.003). Cerebrospinal fluid chitinase 3-like 1 levels were also measured in a second validation clinically isolated syndrome cohort and found to be increased in patients who converted to multiple sclerosis compared with patients who remained as having clinically isolated syndrome (P=0.018). Our results indicate that patients who will convert to clinically definite multiple sclerosis could be distinguished from those patients who will remain as clinically isolated syndrome by proteomic analysis of cerebrospinal fluid samples. Although protein levels are also increased in other disorders characterized by chronic inflammation, chitinase 3-like 1 may serve as a prognostic biomarker for conversion to multiple sclerosis and development of disability which may help to improve the understanding of the aetiopathogenesis in the early stages of multiple sclerosis.
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Immunological mechanisms that associate with oligoclonal IgM band synthesis in multiple sclerosis.
Clin. Immunol.
PUBLISHED: 02-25-2010
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We described previously that multiple sclerosis (MS) patients with oligoclonal IgM against myelin lipids (M+) develop an aggressive disease. Our aim was to assess possible mechanisms regulating the production of these antibodies. We studied B cell subsets in 180 patients with MS, and 69 with other neurological diseases. M+ MS patients showed a moderate increase of CD5(+) B-cell percentage in peripheral blood and a considerable augment of these cells in cerebrospinal fluid (CSF) that correlated with intrathecal IgM production. The appearance of CD5(+) B cells into the central nervous system (CNS) was related to increased CXCL13 and TNF-alpha levels in CSF. Moreover, the presence of oligoclonal IgM associated with a SNP at position -376 of the TNF-alpha promoter. These results help to elucidate the B lymphocytes responsible for intrathecal IgM secretion in MS and the origin of this abnormal B-cell response in patients with aggressive MS.
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Neurofilament ELISA validation.
J. Immunol. Methods
PUBLISHED: 05-03-2009
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Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance.
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CSF oligoclonal band patterns reveal disease heterogeneity in multiple sclerosis.
J. Neuroimmunol.
PUBLISHED: 02-25-2009
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Oligoclonal IgG bands (OCGB) are characteristic of multiple sclerosis (MS). Most patients show OCGB exclusively in cerebrospinal fluid (CSF). Others have serum bands with additional ones in CSF. Moreover, IgM bands against myelin lipids (LS-OCMB) associate with aggressive relapsing-remitting MS (RRMS). We studied oligoclonal bands in 424 MS patients. Most primary progressive (PPMS) patients showed serum OCGB with additional bands in CSF. Conversely, most RRMS and secondary progressive (SPMS) patients showed OCGB exclusively in CSF (p<0.0001). Moreover, no PPMS patient presented LS-OCMB, while 31% of RRMS and 60% of SPMS groups showed these antibodies (p<0.0001). This suggests heterogeneous autoimmune mechanisms in MS.
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Novel cerebrospinal fluid and serum autoantibody targets for clinically isolated syndrome.
J. Neurochem.
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Limited information is available on the identity of antigens targeted by antibodies present in cerebrospinal fluid (CSF) of patients with clinically isolated syndrome (CIS). The aim of this study was to identify novel antigens for CIS and investigate their prognostic potential to predict conversion to multiple sclerosis (MS). We applied serological antigen selection (SAS) to identify antigens interacting with antibodies present in the pooled CSF from four CIS patients, who developed MS. Antibody reactivity towards CIS antigens identified by SAS was tested in CSF and serum from patients with CIS (n = 123/n = 108), MS (n = 65/n = 44), and other (inflammatory) neurological diseases (n = 75/n = 38) as well as in healthy control sera (n = 44). Using SAS, a panel of six novel CIS candidate antigens was identified. CSF antibody reactivity was detected in both CIS and relapsing-remitting (RR) MS. Serum reactivity was significantly increased in CIS and RR-MS as compared with controls (p = 0.03). For two antigens, the frequency of antibody-positive patients was higher in CIS patients who converted to MS as compared with CIS patients without conversion. We identified novel CIS antigens to which antibody reactivity was primarily detected in CIS and RR-MS as compared to controls. Possible prognostic potential could be demonstrated for two antigens.
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A novel molecular mechanism involved in multiple myeloma development revealed by targeting MafB to haematopoietic progenitors.
EMBO J.
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Understanding the cellular origin of cancer can help to improve disease prevention and therapeutics. Human plasma cell neoplasias are thought to develop from either differentiated B cells or plasma cells. However, when the expression of Maf oncogenes (associated to human plasma cell neoplasias) is targeted to mouse B cells, the resulting animals fail to reproduce the human disease. Here, to explore early cellular changes that might take place in the development of plasma cell neoplasias, we engineered transgenic mice to express MafB in haematopoietic stem/progenitor cells (HS/PCs). Unexpectedly, we show that plasma cell neoplasias arise in the MafB-transgenic mice. Beyond their clinical resemblance to human disease, these neoplasias highly express genes that are known to be upregulated in human multiple myeloma. Moreover, gene expression profiling revealed that MafB-expressing HS/PCs were more similar to B cells and tumour plasma cells than to any other subset, including wild-type HS/PCs. Consistent with this, genome-scale DNA methylation profiling revealed that MafB imposes an epigenetic program in HS/PCs, and that this program is preserved in mature B cells of MafB-transgenic mice, demonstrating a novel molecular mechanism involved in tumour initiation. Our findings suggest that, mechanistically, the haematopoietic progenitor population can be the target for transformation in MafB-associated plasma cell neoplasias.
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High levels of cerebrospinal fluid free kappa chains predict conversion to multiple sclerosis.
Clin. Chim. Acta
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A clinically isolated syndrome (CIS) may be the initial presentation of multiple sclerosis (MS). However, some CIS never develop MS. The identification of patients at risk of MS conversion is crucial as early treatment may improve their outcome. Free kappa chains (FKC) are increased in cerebrospinal fluid (CSF) of MS patients. We studied the accuracy of CSF FKC level measurement, using a new nephelometric test, to predict conversion of CIS patients to MS.
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Axonal and oligodendrocyte-localized IgM and IgG deposits in MS lesions.
J. Neuroimmunol.
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Recent findings support the important role of antibodies in multiple sclerosis (MS) physiopathology. Thus, local IgG synthesis is a hallmark of the disease, and intrathecal IgM synthesis associates with a poor disease outcome.
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DRB1*03:01 haplotypes: differential contribution to multiple sclerosis risk and specific association with the presence of intrathecal IgM bands.
PLoS ONE
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Multiple sclerosis (MS) is a multifactorial disease with a genetic basis. The strongest associations with the disease lie in the Human Leukocyte Antigen (HLA) region. However, except for the DRB1*15:01 allele, the main risk factor associated to MS so far, no consistent effect has been described for any other variant. One example is HLA-DRB1*03:01, with a heterogeneous effect across populations and studies. We postulate that those discrepancies could be due to differences in the diverse haplotypes bearing that allele. Thus, we aimed at studying the association of DRB1*03:01 with MS susceptibility considering this allele globally and stratified by haplotypes. We also evaluated the association with the presence of oligoclonal IgM bands against myelin lipids (OCMB) in cerebrospinal fluid.
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Immunological markers of optimal response to natalizumab in multiple sclerosis.
Arch. Neurol.
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To explore cell subsets and molecules that changed specifically in patients with multiple sclerosis (MS) who had an optimal response to natalizumab. Natalizumab is a monoclonal antibody that inhibits the migration of activated immune cells to the central nervous system. It shows high efficacy in modifying the natural history of MS and induces freedom of disease activity in about 40% of treated patients with MS.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.