The Experts below are selected from a list of 78 Experts worldwide ranked by ideXlab platform
Gábor Molnár - One of the best experts on this subject based on the ideXlab platform.
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Naturally occurring human autoantibodies recognize a fetal Brain Antigen identified as microtubulus associated protein 1B.
Life sciences, 2002Co-Authors: Jukka Peltola, Jukka Hellman, Kati Hakkarainen, Aulis Marttinen, Esa Soppi, Gábor MolnárAbstract:We have recently reported naturally occurring autoantibodies against a large fetal Brain Antigen (FBA). Now we describe the process of purification and identification of this particular FBA. The Brains of newborn rabbits were solubilized and purified with preparative gel electrophoresis. The protein fractions were concentrated and desalted and the fractions were tested by a known positive serum. On membrane digestion of the FBA-band gave a twelve amino acid sequence that resulted in best identity score for mouse, rat and human microtubule-associated protein (MAP) 1B: a member of the microtubule-associated protein family. Monoclonal anti-MAP1B recognized a band in immunoblots of the Brain homogenate and of the partially purified fractions with the same electrophoretic mobility as that recognized by a known anti-FBA positive serum. When adult rabbit Brain was used as an Antigen, the anti-MAP1B failed to recognize any bands on immunoblots. MAP lB has not been previously known as an autoAntigen, even though many structural proteins of the neuronal cytoskeleton are known to be targets of naturally occurring autoantibodies. MAP 1B is a functionally important regulatory protein in the developing Brain; thus autoantibodies against MAP1B may affect the normal development.
Stefanie Kuerten - One of the best experts on this subject based on the ideXlab platform.
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The Brain Antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients.
Scientific reports, 2015Co-Authors: Damiano M. Rovituso, Cathrina E. Duffy, Michael Schroeter, Claudia C. Kaiser, Christoph Kleinschnitz, Antonios Bayas, Rebecca Elsner, Stefanie KuertenAbstract:B cells have only recently begun to attract attention in the immunopathology of multiple sclerosis (MS). Suitable markers for the prediction of treatment success with immunomodulatory drugs are still missing. Here we evaluated the B cell response to Brain Antigens in n = 34 relapsing-remitting MS (RRMS) patients treated with glatiramer acetate (GA) using the enzyme-linked immunospot technique (ELISPOT). Our data demonstrate that patients can be subdivided into responders that show Brain-specific B cell reactivity in the blood and patients without this reactivity. Only in patients that classified as B cell responders, there was a significant positive correlation between treatment duration and the time since last relapse in our study. This correlation was GA-specific because it was absent in a control group that consisted of interferon-s (IFN-β)-treated RRMS patients (n = 23). These data suggest that GA has an effect on Brain-reactive B cells in a subset of patients and that only this subset benefits from treatment. The detection of Brain-reactive B cells is likely to be a suitable tool to identify drug responders.
Jean-françois Ghersi-egea - One of the best experts on this subject based on the ideXlab platform.
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Brain leukocyte infiltration initiated by peripheral inflammation or experimental autoimmune encephalomyelitis occurs through pathways connected to the CSF-filled compartments of the foreBrain and midBrain
Journal of Neuroinflammation, 2012Co-Authors: Charlotte Schmitt, Nathalie Strazielle, Jean-françois Ghersi-egeaAbstract:Background Cerebrospinal fluid (CSF) has been considered as a preferential pathway of circulation for immune cells during neuroimmune surveillance. In order to evaluate the involvement of CSF-filled spaces in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, we performed a time-course analysis of immune cell association with the CSF-containing ventricles, velae, and cisterns in two active models of this disease. Methods Guinea-pig spinal cord homogenate-induced EAE in rat and myelin oligodendrocyte glycoprotein-induced EAE in mouse were used. Leukocyte distribution and phenotypes were investigated by immunohistochemistry in serial sections of Brain areas of interest, as well as in CSF withdrawn from rat. Immune cells associated with the choroid plexuses were quantified. Results Freund’s adjuvant-induced peripheral inflammation in the absence of Brain Antigen led to a subtle but definite increase in the number of myeloid cells in the extraventricular CSF spaces. In both rats and mice, EAE was characterized by a sustained and initial infiltration of lymphocytes and monocytes within foreBrain/midBrain fluid-filled compartments such as the velum interpositum and ambient cisterns, and certain basal cisterns. Leukocytes further infiltrated periventricular and pericisternal parenchymal areas, along perivascular spaces or following a downward CSF-to-tissue gradient. Cells quantified in CSF sampled from rats included lymphocytes and neutrophils. The distinctive pattern of cell distribution suggests that both the choroid plexus and the vessels lying in the velae and cisterns are gates for early leukocyte entry in the central nervous system. B-cell infiltration observed in the mouse model was restricted to CSF-filled extraventricular compartments. Conclusion These results identified distinctive velae and cisterns of the foreBrain and midBrain as preferential sites of immune cell homing following peripheral and early central inflammation and point to a role of CSF in directing Brain invasion by immune cells during EAE.
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Brain leukocyte infiltration initiated by peripheral inflammation or experimental autoimmune encephalomyelitis occurs through pathways connected to the CSF-filled compartments of the foreBrain and midBrain.
Journal of Neuroinflammation, 2012Co-Authors: Charlotte Schmitt, Nathalie Strazielle, Jean-françois Ghersi-egeaAbstract:UNLABELLED: ABSTRACT: BACKGROUND: Cerebrospinal fluid (CSF) has been considered as a preferential pathway of circulation for immune cells during neuroimmune surveillance. In order to evaluate the involvement of CSF-filled spaces in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, we performed a time-course analysis of immune cell association with the CSF-containing ventricles, velae, and cisterns in two active models of this disease. METHODS: Guinea-pig spinal cord homogenate-induced EAE in rat and myelin oligodendrocyte glycoprotein-induced EAE in mouse were used. Leukocyte distribution and phenotypes were investigated by immunohistochemistry in serial sections of Brain areas of interest, as well as in CSF withdrawn from rat. Immune cells associated with the choroid plexuses were quantified. RESULTS: Freund's adjuvant-induced peripheral inflammation in the absence of Brain Antigen led to a subtle but definite increase in the number of myeloid cells in the extraventricular CSF spaces. In both rats and mice, EAE was characterized by a sustained and initial infiltration of lymphocytes and monocytes within foreBrain/midBrain fluid-filled compartments such as the velum interpositum and ambient cisterns, and certain basal cisterns. Leukocytes further infiltrated periventricular and pericisternal parenchymal areas, along perivascular spaces or following a downward CSF-to-tissue gradient. Cells quantified in CSF sampled from rats included lymphocytes and neutrophils. The distinctive pattern of cell distribution suggests that both the choroid plexus and the vessels lying in the velae and cisterns are gates for early leukocyte entry in the central nervous system. B-cell infiltration observed in the mouse model was restricted to CSF-filled extraventricular compartments. CONCLUSION: These results identified distinctive velae and cisterns of the foreBrain and midBrain as preferential sites of immune cell homing following peripheral and early central inflammation and point to a role of CSF in directing Brain invasion by immune cells during EAE.
Steffen Jung - One of the best experts on this subject based on the ideXlab platform.
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gatekeeper role of Brain Antigen presenting cd11c cells in neuroinflammation
The EMBO Journal, 2016Co-Authors: Magdalena Paterka, Volker Siffrin, Jan Oliver Voss, Johannes Werr, Nicola Hoppmann, René Gollan, Patrick Belikan, Julia Bruttger, Jérôme Birkenstock, Steffen JungAbstract:Abstract Multiple sclerosis is the most frequent chronic inflammatory disease of the CNS. The entry and survival of pathogenic T cells in the CNS are crucial for the initiation and persistence of autoimmune neuroinflammation. In this respect, contradictory evidence exists on the role of the most potent type of Antigen‐presenting cells, dendritic cells. Applying intravital two‐photon microscopy, we demonstrate the gatekeeper function of CNS professional Antigen‐presenting CD11c + cells, which preferentially interact with Th17 cells. IL‐17 expression correlates with expression of GM‐CSF by T cells and with accumulation of CNS CD11c + cells. These CD11c + cells are organized in perivascular clusters, targeted by T cells, and strongly express the inflammatory chemokines Ccl5 , Cxcl9 , and Cxcl10 . Our findings demonstrate a fundamental role of CNS CD11c + cells in the attraction of pathogenic T cells into and their survival within the CNS. Depletion of CD11c + cells markedly reduced disease severity due to impaired enrichment of pathogenic T cells within the CNS.
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Gatekeeper role of Brain Antigen‐presenting CD11c + cells in neuroinflammation
The EMBO journal, 2015Co-Authors: Magdalena Paterka, Volker Siffrin, Jan Oliver Voss, Johannes Werr, Nicola Hoppmann, René Gollan, Patrick Belikan, Julia Bruttger, Jérôme Birkenstock, Steffen JungAbstract:Abstract Multiple sclerosis is the most frequent chronic inflammatory disease of the CNS. The entry and survival of pathogenic T cells in the CNS are crucial for the initiation and persistence of autoimmune neuroinflammation. In this respect, contradictory evidence exists on the role of the most potent type of Antigen‐presenting cells, dendritic cells. Applying intravital two‐photon microscopy, we demonstrate the gatekeeper function of CNS professional Antigen‐presenting CD11c + cells, which preferentially interact with Th17 cells. IL‐17 expression correlates with expression of GM‐CSF by T cells and with accumulation of CNS CD11c + cells. These CD11c + cells are organized in perivascular clusters, targeted by T cells, and strongly express the inflammatory chemokines Ccl5 , Cxcl9 , and Cxcl10 . Our findings demonstrate a fundamental role of CNS CD11c + cells in the attraction of pathogenic T cells into and their survival within the CNS. Depletion of CD11c + cells markedly reduced disease severity due to impaired enrichment of pathogenic T cells within the CNS.
Jukka Peltola - One of the best experts on this subject based on the ideXlab platform.
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Naturally occurring human autoantibodies recognize a fetal Brain Antigen identified as microtubulus associated protein 1B.
Life sciences, 2002Co-Authors: Jukka Peltola, Jukka Hellman, Kati Hakkarainen, Aulis Marttinen, Esa Soppi, Gábor MolnárAbstract:We have recently reported naturally occurring autoantibodies against a large fetal Brain Antigen (FBA). Now we describe the process of purification and identification of this particular FBA. The Brains of newborn rabbits were solubilized and purified with preparative gel electrophoresis. The protein fractions were concentrated and desalted and the fractions were tested by a known positive serum. On membrane digestion of the FBA-band gave a twelve amino acid sequence that resulted in best identity score for mouse, rat and human microtubule-associated protein (MAP) 1B: a member of the microtubule-associated protein family. Monoclonal anti-MAP1B recognized a band in immunoblots of the Brain homogenate and of the partially purified fractions with the same electrophoretic mobility as that recognized by a known anti-FBA positive serum. When adult rabbit Brain was used as an Antigen, the anti-MAP1B failed to recognize any bands on immunoblots. MAP lB has not been previously known as an autoAntigen, even though many structural proteins of the neuronal cytoskeleton are known to be targets of naturally occurring autoantibodies. MAP 1B is a functionally important regulatory protein in the developing Brain; thus autoantibodies against MAP1B may affect the normal development.