Weber, Martin S.

[["dc.bibliographiccitation.artnumber","218"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","20"],["dc.contributor.affiliation","Häusler, Darius; \t\t \r\n\t\t Institute of Neuropathology, University Medical Center, 37099 Göttingen, Germany, darius.haeusler@med.uni-goettingen.de"],["dc.contributor.affiliation","Weber, Martin S.; \t\t \r\n\t\t Institute of Neuropathology, University Medical Center, 37099 Göttingen, Germany, martin.weber@med.uni-goettingen.de\t\t \r\n\t\t Department of Neurology, University Medical Center, 37099 Göttingen, Germany, martin.weber@med.uni-goettingen.de"],["dc.contributor.author","Häusler, Darius"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2019-07-09T11:49:57Z"],["dc.date.available","2019-07-09T11:49:57Z"],["dc.date.issued","2019"],["dc.date.updated","2022-09-06T14:14:55Z"],["dc.description.abstract","The exact cause of multiple sclerosis (MS) remains elusive. Various factors, however, have been identified that increase an individual's risk of developing this central nervous system (CNS) demyelinating disease and are associated with an acceleration in disease severity. Besides genetic determinants, environmental factors are now established that influence MS, which is of enormous interest, as some of these contributing factors are relatively easy to change. In this regard, a low vitamin D status is associated with an elevated relapse frequency and worsened disease course in patients with MS. The most important question, however, is whether this association is causal or related. That supplementing vitamin D in MS is of direct therapeutic benefit, is still a matter of debate. In this manuscript, we first review the potentially immune modulating mechanisms of vitamin D, followed by a summary of current and ongoing clinical trials intended to assess whether vitamin D supplementation positively influences the outcome of MS. Furthermore, we provide emerging evidence that excessive vitamin D treatment via the T cell-stimulating effect of secondary hypercalcemia, could have negative effects in CNS demyelinating disease. This jointly merges into the balancing concept of a therapeutic window of vitamin D in MS."],["dc.identifier.doi","10.3390/ijms20010218"],["dc.identifier.pmid","30626090"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15815"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59662"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1422-0067"],["dc.relation.issn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Vitamin D Supplementation in Central Nervous System Demyelinating Disease-Enough Is Enough"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Häusler, Darius"],["dc.contributor.author","Torke, Sebastian"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2021-04-14T08:26:59Z"],["dc.date.available","2021-04-14T08:26:59Z"],["dc.date.issued","2020"],["dc.description.abstract","The exact cause of multiple sclerosis (MS) is unknown; however, it is considered to be an inflammatory disease of the central nervous system (CNS) triggered by a combination of both environmental and genetic factors. Vitamin D deficiency is also discussed as a possible disease-promoting factor in MS, as low vitamin D status is associated with increased formation of CNS lesions, elevated number of relapses and accelerated disease progression. However, it remains unclear whether this association is causal and related and most importantly, whether vitamin D supplementation in MS is of direct therapeutic benefit. Recently, we could show that in a murine model of MS, administration of a moderate vitamin D dose was of clinical benefit, while excessive vitamin D supplementation had a negative effect on disease severity. Of note, disease exacerbation was associated with high-dose vitamin D caused secondary hypercalcemia. Mechanistically dissecting this outcome, we found that hypercalcemia independent of vitamin D similarly triggered activation of disease-perpetuating T cells. These findings caution that vitamin D should be supplemented in a controlled and moderate manner in patients with MS and concomitantly highlight calcium as a novel potential MS risk factor by itself. In this review, we will summarize the current evidence from animal and clinical studies aiming to assess whether vitamin D may be of benefit in patients with MS. Furthermore, we will discuss any possible secondary effects of vitamin D with a particular focus on the role of calcium on immune cells and in the pathogenesis of CNS demyelinating disease."],["dc.identifier.doi","10.3389/fimmu.2020.00301"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82135"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-3224"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","High-Dose Vitamin D-Mediated Hypercalcemia as a Potential Risk Factor in Central Nervous System Demyelinating Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e698"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neurology - Neuroimmunology Neuroinflammation"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Häusler, Darius"],["dc.contributor.author","Hajiyeva, Zivar"],["dc.contributor.author","Traub, Jan W."],["dc.contributor.author","Zamvil, Scott S."],["dc.contributor.author","Lalive, Patrice H."],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2021-04-14T08:26:30Z"],["dc.date.available","2021-04-14T08:26:30Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1212/NXI.0000000000000698"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81971"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","2332-7812"],["dc.title","Glatiramer acetate immune modulates B-cell antigen presentation in treatment of MS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e10"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Brain: A Journal of Neurology"],["dc.bibliographiccitation.lastpage","e10"],["dc.bibliographiccitation.volume","143"],["dc.contributor.author","Häusler, Darius"],["dc.contributor.author","Torke, Sebastian"],["dc.contributor.author","Peelen, Evelyn"],["dc.contributor.author","Bertsch, Thomas"],["dc.contributor.author","Weber, Matthias"],["dc.contributor.author","Heilmann, Marcus"],["dc.contributor.author","Djukic, Marija"],["dc.contributor.author","Nau, Roland"],["dc.contributor.author","Larochelle, Catherine"],["dc.contributor.author","Zamvil, Scott S"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Weber, Martin S"],["dc.date.accessioned","2021-04-14T08:27:32Z"],["dc.date.available","2021-04-14T08:27:32Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1093/brain/awz389"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82322"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1460-2156"],["dc.relation.issn","0006-8950"],["dc.title","Reply: Neither human nor mouse is hypercalcaemic with 250 nmol/l 25-hydroxyvitamin D"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","535"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","548"],["dc.bibliographiccitation.volume","140"],["dc.contributor.author","Torke, Sebastian"],["dc.contributor.author","Pretzsch, Roxanne"],["dc.contributor.author","Häusler, Darius"],["dc.contributor.author","Haselmayer, Philipp"],["dc.contributor.author","Grenningloh, Roland"],["dc.contributor.author","Boschert, Ursula"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2021-04-14T08:24:46Z"],["dc.date.available","2021-04-14T08:24:46Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1007/s00401-020-02204-z"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81418"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.title","Inhibition of Bruton’s tyrosine kinase interferes with pathogenic B-cell development in inflammatory CNS demyelinating disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9773"],["dc.bibliographiccitation.issue","39"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","9778"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Häusler, Darius"],["dc.contributor.author","Häusser-Kinzel, Silke"],["dc.contributor.author","Feldmann, Linda"],["dc.contributor.author","Torke, Sebastian"],["dc.contributor.author","Lepennetier, Gildas"],["dc.contributor.author","Bernard, Claude C. A."],["dc.contributor.author","Zamvil, Scott S."],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Lehmann-Horn, Klaus"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2021-06-01T10:51:05Z"],["dc.date.available","2021-06-01T10:51:05Z"],["dc.date.issued","2018"],["dc.description.abstract","The anti-CD20 antibody ocrelizumab, approved for treatment of multiple sclerosis, leads to rapid elimination of B cells from the blood. The extent of B cell depletion and kinetics of their recovery in different immune compartments is largely unknown. Here, we studied how anti-CD20 treatment influences B cells in bone marrow, blood, lymph nodes, and spleen in models of experimental autoimmune encephalomyelitis (EAE). Anti-CD20 reduced mature B cells in all compartments examined, although a subpopulation of antigen-experienced B cells persisted in splenic follicles. Upon treatment cessation, CD20 + B cells simultaneously repopulated in bone marrow and spleen before their reappearance in blood. In EAE induced by native myelin oligodendrocyte glycoprotein (MOG), a model in which B cells are activated, B cell recovery was characterized by expansion of mature, differentiated cells containing a high frequency of myelin-reactive B cells with restricted B cell receptor gene diversity. Those B cells served as efficient antigen-presenting cells (APCs) for activation of myelin-specific T cells. In MOG peptide-induced EAE, a purely T cell-mediated model that does not require B cells, in contrast, reconstituting B cells exhibited a naive phenotype without efficient APC capacity. Our results demonstrate that distinct subpopulations of B cells differ in their sensitivity to anti-CD20 treatment and suggest that differentiated B cells persisting in secondary lymphoid organs contribute to the recovering B cell pool."],["dc.identifier.doi","10.1073/pnas.1810470115"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86889"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.title","Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","834"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","839"],["dc.bibliographiccitation.volume","90"],["dc.contributor.affiliation","Quendt, Corinna; 1\r\nDepartment of Neurology\r\nUniversity Medical Center\r\nGöttingen Germany"],["dc.contributor.affiliation","Ochs, Jasmin; 2\r\nInstitute of Neuropathology\r\nUniversity Medical Center\r\nGöttingen Germany"],["dc.contributor.affiliation","Häusser‐Kinzel, Silke; 2\r\nInstitute of Neuropathology\r\nUniversity Medical Center\r\nGöttingen Germany"],["dc.contributor.affiliation","Häusler, Darius; 2\r\nInstitute of Neuropathology\r\nUniversity Medical Center\r\nGöttingen Germany"],["dc.contributor.author","Quendt, Corinna"],["dc.contributor.author","Ochs, Jasmin"],["dc.contributor.author","Häusser‐Kinzel, Silke"],["dc.contributor.author","Häusler, Darius"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2021-12-01T09:23:20Z"],["dc.date.available","2021-12-01T09:23:20Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-20T23:49:05Z"],["dc.description.abstract","The frequency of CD20+ T cells was reported to be increased in several inflammatory conditions. We report that in patients with multiple sclerosis (MS), CD20+ T cells display a distinct proinflammatory phenotype with pathogenic properties. Anti‐CD20 treatment virtually extinguished CD20+ T cells, which might explain its broad effectiveness. Dimethyl fumarate dampened activity of differentiated CD20+ T cells, whereas fingolimod reduced their abundance only as part of its overall T cell suppressive capacity. Natalizumab increased the frequency of CD20+ effector T cells. Widely used MS therapeutics affect this proinflammatory T cell subset with assumed pathogenic potential in a surprisingly differential manner. ANN NEUROL 2021 ANN NEUROL 2021;90:834–839"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","National Multiple Sclerosis Society http://dx.doi.org/10.13039/100000890"],["dc.identifier.doi","10.1002/ana.26216"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94621"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","1531-8249"],["dc.relation.issn","0364-5134"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made."],["dc.title","Proinflammatory CD20 + T Cells are Differentially Affected by Multiple Sclerosis Therapeutics"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3461"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.affiliation","Geladaris, Anastasia; \t\t \r\n\t\t Department of Neuropathology, University Medical Center, 37075 Göttingen, Germany, anastasia.geladaris@med.uni-goettingen.de"],["dc.contributor.affiliation","Häusler, Darius; \t\t \r\n\t\t Department of Neuropathology, University Medical Center, 37075 Göttingen, Germany, darius.haeusler@med.uni-goettingen.de"],["dc.contributor.affiliation","Weber, Martin S.; \t\t \r\n\t\t Department of Neuropathology, University Medical Center, 37075 Göttingen, Germany, martin.weber@med.uni-goettingen.de\t\t \r\n\t\t Department of Neurology, University Medical Center, 37075 Göttingen, Germany, martin.weber@med.uni-goettingen.de"],["dc.contributor.author","Geladaris, Anastasia"],["dc.contributor.author","Häusler, Darius"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2021-06-01T09:42:36Z"],["dc.date.available","2021-06-01T09:42:36Z"],["dc.date.issued","2021"],["dc.date.updated","2022-09-06T04:04:15Z"],["dc.description.abstract","Therapeutically controlling chronic progression in multiple sclerosis (MS) remains a major challenge. MS progression is defined as a steady loss of parenchymal and functional integrity of the central nervous system (CNS), occurring independent of relapses or focal, magnetic resonance imaging (MRI)-detectable inflammatory lesions. While it clinically surfaces in primary or secondary progressive MS, it is assumed to be an integral component of MS from the very beginning. The exact mechanisms causing progression are still unknown, although evolving evidence suggests that they may substantially differ from those driving relapse biology. To date, progression is assumed to be caused by an interplay of CNS-resident cells and CNS-trapped hematopoietic cells. On the CNS-resident cell side, microglia that are phenotypically and functionally related to cells of the monocyte/macrophage lineage may play a key role. Microglia function is highly transformable. Depending on their molecular signature, microglia can trigger neurotoxic pathways leading to neurodegeneration, or alternatively exert important roles in promoting neuroprotection, downregulation of inflammation, and stimulation of repair. Accordingly, to understand and to possibly alter the role of microglial activation during MS disease progression may provide a unique opportunity for the development of suitable, more effective therapeutics. This review focuses on the current understanding of the role of microglia during disease progression of MS and discusses possible targets for therapeutic intervention."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3390/ijms22073461"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17852"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85297"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1422-0067"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Microglia: The Missing Link to Decipher and Therapeutically Control MS Progression?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]