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February 2022 – The Beltrán and Gerdes labs studied the immune profiles in the MS TWIN STUDY to differentiate the influence of the environment and genetics in multiple sclerosis. In collaboration with the Becher lab from the University of Zurich they may have discovered precursor cells of the disease-causing T cells.

The impact of genetic risk has been studied for years, however the genetic background is far from deterministic and interaction with environmental factors is needed for MS to evolve. However, which part of the aberrant immune response is guided by either genes or environment is difficult to decipher. With the help of the unique setting of the MS TWIN STUDY we could show that about half of the composition of our immune system is determined by the genetic background. In this project, peripheral blood mononuclear cells of 61 pairs of identical twins with discordance for MS were examined with the use of cutting-edge single-cell technologies and artificial intelligence to describe the immune profiles of the twin pairs in rich detail and with full control of genetic influences. Thereby we could not only identify characteristic proteins in the immune cells of the MS affected twin, but also decode which transcriptional programs are switched on in these cells. Specifically, in the blood of MS twins we detected T cells with characteristics of recently activated cells, which are more likely to migrate into the central nervous system and cause damage there.

November 2021 – Progressive multifocal leukoencephalopathy (PML) is a severe CNS infection that can occur in MS patients treated with Natalizumab. Clinical management of patients with Natalizumab-associated PML is challenging not least to detect, monitor and differentiate PML lesions are limited. Here the Kerschensteiner lab and Kümpfel group teamed up to investigate whether TSPO PET imaging can be applied to monitor the inflammatory activity of PML lesions over time. The results of this monocentre pilot study now indicate that TSPO PET imaging may faciliate longitudinal monitoring of disease activity and help distinguish recurrent multiple sclerosis activity from PML progression.

June 2021 – Nerve cells in the brain possess small protrusions, so called dendritic spines, to communicate with other nerve cells by forming a synapse. These contact sites can be both, short- or long-lived thereby existing for even up to an entire lifetime. Short-lived contact sites reflect an ever- adapting brain, which is necessary to process novel experiences. Long-lived, stable contact sites, on the other hand, form the basis of our memory. But even stable memory content can vary to some extent over time. The basis of this process still remains incompletely understood. The work, published in the journal Science Advances, shows that although a subset of synaptic structures remain present at the same location over a period of at least one month, their subunits underwent a remarkable and unexpected strong change in size and shape. Synaptic structures are thus both stable and dynamic – 'volatile' – at the same time, offering a glimpse into the complexity of synaptic remodelling and computational power mammalian brains are endowed with. Press release

June 2021 – Antibodies (Abs) to myelin oligodendrocyte glycoprotein (MOG) define a distinct disease entity, MOGAD. We report that the intracellular part of MOG, specifically its second hydrophobic domain enhances the recognition of the extracellular part of MOG by autoantibodies from patients. This explains the need for a cell-based assay to identify patients with MOG-Abs. We further found that MOG-Abs from patients require bivalent binding to recognize MOG. Since bivalently bound MOG-Abs poorly bind C1q, this indicates that complement-mediated demyelination is not the major pathomechanism of MOG-Abs.

June 2021 – The Liebscher lab together with the Dupuis group in Strasbourg, France and a highly collaborative international team of several other groups have found the missing pieces between genetic mutations linked to the development of Amyotrophic lateral sclerosis and Frontotemporal Dementia and the consecutive behavioral deficits. Using a wide array of methodological approaches they found that cytoplasmic mislocalization of the protein Fused-in-Sarcoma (FUS) causes its synaptic accumulation and local transcriptional dysregulation, leading to synaptic deficits of primarily inhibitory synapses in frontal cortex, which is causing neuronal hyperexcitability and consequently behavioral alterations. These data thus indicate that cytoplasmic FUS can excert deleterious effects beyond motor neuron degeneration, which are mainly caused by synaptic alterations.

Jelena Scekic-Zahirovic*, Inmaculada Sanjuan-Ruiz*, Vanessa Kan, Salim Megat, Pierre De Rossi, Stéphane Dieterlé, Raphaelle Cassel, Marguerite Jamet, Pascal Kessler, Diana Wiesner, Laura Tzeplaeff, Valérie Demais, Sonu Sahadevan, Katharina M. Hembach, Hans-Peter Muller, Gina Picchiarelli, Nibha Mishra, Stefano Antonucci, Sylvie Dirrig-Grosch, Jan Kassubek, Volker Rasche, Albert Ludolph, Anne-Laurence Boutillier, Francesco Roselli, Magdalini Polymenidou, Clotilde Lagier-Tourenne, Sabine Liebscher# and Luc Dupuis#, Cytoplasmic FUS triggers early behavioral alterations linked to cortical neuronal hyperactivity and inhibitory synaptic defects, Nature Communications, 2021,12:3028

March 2021 – The Dornmair group together with the Meuth/Melzer group from Münster, Germany and several other colleagues investigated antibodies recognizing the neuronal gamma-aminobutyric-acid-A receptor (GABAA-R), which cause severe encephalitis. From the cerebrospinal fluid of a patient with GABAA–R encephalitis, they cloned a highly expressed antibody and showed that it binds the GABAA-R and influences signal transduction in neurons explaining clinical symptoms. They confirmed that the antibody cross-reacts to an onco-protein, which is known to be involved in several malignancies and showed that cross-reactivity to this onco-protein may also be detected in two other GABAA-R patients. This suggests that such cross-reactivity is presumably a key event in the pathogenesis of GABAA-R encephalitis.

January 2021 – Gray matter pathology is a critical contributor to disability in advanced stages of multiple sclerosis. Here the Kerschensteiner lab teamed up with the Misgeld and Merkler lab to investigate how neuronal structure and function is impacted in the neuronal gray matter. In a mouse model they show that gray matter inflammation leads to a synapse loss that is accompagnied by neuronal silencing and can be reversible. Synapse loss is primed by local calcium increases, executed by activated microglial cells and infiltrating monocyte-derived macrophages and can be mitigated by therapeutic strategies that interfer with pathological activation of phagocytes. The authors hope that their work can help the development of therapeutic approaches that curb progression in MS patients.

January 2021 – The Dornmair group together with the Lassmann/Bradl group from the Medical University of Vienna and colleagues of the Meinl and Kawakami groups analyzed a historic case of a patient who died 60 years ago from a disease closely resembling multiple sclerosis, following a misguided immunization with lyophilized calf brain tissue. Transcriptome analyses by mRNAseq and antibody reconstruction by bioinformatics revealed an autoantibody (rAb-hAE) against myelin oligodendrocytes glycoprotein (MOG), similar to the encephalitogenic anti-MOG antibody 8-18C5. Both antibodies induced demyelination after injection into animals, whereas the negative control antibody rMS3-s1 did not. This “archeological neuroimmunology” approach shows that autoimmunization with brain tissue in humans may induce a disease that is similar to multiple sclerosis.

September 2020 – To interrogate the rules that govern myelin replacement in the cortex the Kerschensteiner group together with the Misgeld lab at TUM studied the response to the ablation of single cortical oligodendrocytes. Using timelapse imaging and correlated ultrastructural reconstructions they were able to show that a loss of a single oligodendrocyte is sufficient to cause robust cell and myelin replacement. In this process internodes along partially myelinated axons were typically not reestablished, while myelin sheaths forming continuous patterns showed remarkable homeostatic resiliences and remyelinated with single axon precision. Understanding these principles is particularly important in the context of multiple sclerosis which extensive cortical demyelination is a major pathological feature and target of remyelination therapies.

September 2020 – In this study we used our unique setting of the MS TWIN STUDY to explore the peripheral immune signature in collaboration with the UK Münster. In each twin pair, the immune signatures were remarkably similar, pointing to a strong influence of shared genetic and environmental factors. However, when we focused on a subgroup of seemingly healthy cotwins who showed subtle signs of “subclinical neuro-inflammation,” we identified a distinct signature of memory T cells.

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Commentary

November 2019 – Here we report on the principles that drive functional circuit remodeling following spinal cord injury. We demonstrate in this paper that functional circuit remodeling critically depends on the selection of appropriate synaptic connections between cortical projection and spinal relay neurons. In particular, we use in this paper a combination of genetic and chemogenetic tools to modulate NMDA receptor (NMDAR) integrity and function, CREB-mediated transcription, and neuronal firing of relay neurons during injury-induced corticospinal remodeling. We show that NMDAR signaling and CREB-mediated transcription maintain nascent corticospinal tract (CST)–relay neuron contacts. These activity-dependent signals act during a defined period of circuit remodeling and do not affect mature or uninjured circuits. Furthermore, chemogenetic modulation of relay neuron activity reveals that the regrowing CST axons select their postsynaptic partners in a competitive manner and that preventing such activity-dependent shaping of corticospinal circuits limits motor recovery after spinal cord injury.

November 2019 – The early immunological events that drive MS are still enigmatic. To add a piece to the jigsaw we analyzed CSF samples of a unique selection of our MS TWIN STUDY. Using single-cell RNA sequencing we identified clonally expanded CD8+ T cells, plasmablasts, and, to a lesser extent, CD4+ T cells not only from MS co-twins but also from clinical healthy co-twins with signs of subclinical neuroinflammation as detected on MRI and/or CSF. Strikingly, clonally expanded T cells showed characteristics of activated tissue-resident memory T (TRM) cells and were already detectable in prodromal stages but more pronounced in patients with definite MS. Our data provide evidence for very early concomitant activation of 3 components of the adaptive immune system in MS, with a notable contribution of clonally expanded TRM-like CD8+ cells.

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Februar 2019 – To reveal the mechanisms that drive inflammatory axon degeneration the Kerschensteiner lab has used in vivo calcium imaging in a multiple sclerosis model. Dynamic tracking of individual axons in the inflamed spinal cord shows that cytoplasmic calcium levels determine the choice between axon loss and survival. Calcium can enter the axon through nanoscale ruptures of the axonal plasma membrane that are induced in inflammatory lesions. These results thus identify a unusual axon injury pathway that can contribute to neurodegeneration in multiple sclerosis and may represent a novel target for protective therapy.

Press Release

May 2019 – The modest concordance rate for MS in monozygotic twins strongly argues for involvement of epigenetic factors. To check the contribution of epigenetic modifications we looked at the methylomes of 45 pairs from the MS TWIN STUDY together with our collaborators Nicole Souren and Jörn Walter, Saarland Universtiy. We identified seven MS-associated differentially methylated positions (DMPs) of which we validated two, including a region in the TMEM232 promoter and ZBTB16 enhancer. Not expected but not of less relevance we presented epigenetic biomarkers for current interferon-beta treatment, and that the ZBTB16 DMP is a signature for prior glucocorticoid treatment. Taken together, this study represents an important reference for epigenomic MS studies, identifies new candidate epigenetic markers, and highlights treatment effects and genetic background as major confounders.

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August 2018 –Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) can be detected in the blood of a proportion of patients with inflammatory demyelinating diseases of the CNS. We affinity-purified MOG-Abs from the blood of two patients. These anti-MOG Abs were pathogenic upon transfer into rats and we could dissect two different mechanisms by which these MOG-Abs enhanced pathology. First, together with cognate MOG-specific T cells, these Abs enhanced T cell infiltration; Second, together with MBP-specific T cells that strongly breach the blood-brain barrier, these MOG-Abs induced demyelination associated with deposition of C9neo, resembling a multiple sclerosis type II pathology. This suggests that MOG-Abs are similarly pathogenic in patients.

Februar 2018 – Mononuclear phagocytes can both promote and inhibit inflammation. Here the Kerschensteiner lab uses an in vivo imaging approach to follow the evolution of phagocyte phenotypes in neuroinflammatory lesions. By tracking phagocytes over time they can show that individual phagocytes switch their phenotype as lesions move from expansion to resolution. This phenotype shift appears to be initiated by signals derived from the nervous system tissue. Understanding the molecular nature of these signals might thus provide the basis for therapeutic manipulation of phagocyte function in the inflamed CNS.

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August 2017 – Studies using experimental models have indicated that MS like disease can be triggered in the gut following interactions of brain autoimmune T lymphocytes with local microbiota. In this key paper, we studied the composition of the gut microbiota in our MS TWIN STUDY and in addition transferred human-derived microbiota into transgenic mice expressing a myelin autoantigen-specific T cell receptor. Strikingly, we detected that gut microbiota from MS-affected twins induced CNS-specific autoimmunity at a higher incidence than microbiota from healthy co-twins. Our results offered functional evidence that human microbiome components contribute to CNS-specific autoimmunity and opened up the field for further studies of the gut microbiome in MS.

Press Release

Awarded for highlights of MPG Research 2017

November 2016 – Damage to oligodendrocytes and their myelin sheaths is a central feature of multiple sclerosis pathology. Here the Kerschensteiner lab investigates how oligodendrocyte damage is initiated in multiple sclerosis (MS) and EAE using in vivo imaging, confocal microscopy as well as electron microscopy. They can show that oligodendrocyte damage spreads centripetally and that the formation of focal myelin outfoldings that they call “myelinosomes” is an early sign of oligodendrocyte damage both in MS and EAE…

January 2016 – How neurodegeneration starts in the brains of progressive multiple sclerosis patients is only incompletely understood. Here the Kerschensteiner lab joined forces with the Merkler lab at the University of Genevan and used confocal microscopy of Golgi-Cox impregnated tissue sections to reconstruct single cortical projection neurons in brain sections from multiple sclerosis and control patients. Their study reveals a widespread and pronounced loss of dendritic spines that occurs independently of cortical demyelination and axon loss and indicates the presence of a primary synaptic pathology in multiple sclerosis…

May 2015 – Following spinal cord injury, transected projections form detour circuits that circumvent the lesion and contribute to functional recovery. The formation of new synaptic contacts is a crucial step of the process, but its molecular regulation is currently not understood. Members of the FGF family can promote synapse formation during nervous system development, suggesting that they might have a similar function in the injured adult CNS. Here, we show that: (i) FGF22 and FGF22 receptors are expressed in the adult nervous system. (ii) FGF22 deficiency or deletion of FGF22 receptors restricts the formation and maturation of new synapses in the injured spinal cord. (iii) Genetic disruption of FGF22 signaling impedes spontaneous functional recovery following spinal cord injury

Lana-Peixoto MA, Fontenelle MA, Ashtari F, Kafieh R, Dehghani A, Pourazizi M, Pandit L, D'Cunha A, Kim HJ, Hyun JW, Jung SK, Leocani L, Pisa M, Radaelli M, Siritho S, May EF, Tongco C, De Sèze J, Senger T, Palace J, Roca-Fernández A, Leite MI, Sharma SM, Stiebel-Kalish H, Asgari N, Soelberg KK, Martinez-Lapiscina EH, Havla J, Mao-Draayer Y, Rimler Z, Reid A, Marignier R, Cobo-Calvo A, Altintas A, Tanriverdi U, Yildirim R, Aktas O, Ringelstein M, Albrecht P, Tavares IM, Bichuetti DB, Jacob A, Huda S, Soto de Castillo I, Petzold A, Green AJ, Yeaman MR, Smith TJ, Cook L, Paul F, Brandt AU, Oertel FC; GJCF International Clinical Consortium for NMOSD. Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders. J Neurol Neurosurg Psychiatry. 2021 Oct 28:jnnp-2021-327412.

Ostkamp P, Salmen A, Pignolet B, Görlich D, Andlauer TFM, Schulte-Mecklenbeck A, Gonzalez-Escamilla G, Bucciarelli F, Gennero I, Breuer J, Antony G, Schneider-Hohendorf T, Mykicki N, Bayas A, Then Bergh F, Bittner S, Hartung HP, Friese MA, Linker RA, Luessi F, Lehmann-Horn K, Mühlau M, Paul F, Stangel M, Tackenberg B, Tumani H, Warnke C, Weber F, Wildemann B, Zettl UK, Ziemann U, Müller-Myhsok B, Kümpfel T, Klotz L, Meuth SG, Zipp F, Hemmer B, Hohlfeld R, Brassat D, Gold R, Gross CC, Lukas C, Groppa S, Loser K, Wiendl H, Schwab N; German Competence Network Multiple Sclerosis (KKNMS) and the BIONAT Network. Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity. Proc Natl Acad Sci U S A. 2021 Jan 5;118(1):e2018457118.

Ayzenberg I, Richter D, Henke E, Asseyer S, Paul F, Trebst C, Hümmert MW, Havla J, Kümpfel T, Ringelstein M, Aktas O, Wildemann B, Jarius S, Häußler V, Stellmann JP, Senel M, Klotz L, Pellkofer HL, Weber MS, Pawlitzki M, Rommer PS, Berthele A, Wernecke KD, Hellwig K, Gold R, Kleiter I; NEMOS (Neuromyelitis Optica Study Group). Pain, Depression, and Quality of Life in Neuromyelitis Optica Spectrum Disorder: A Cross-Sectional Study of 166 AQP4 Antibody-Seropositive Patients. Neurol Neuroimmunol Neuroinflamm. 2021 Apr 20;8(3):e985.

Dürr M, Nissen G, Sühs KW, Schwenkenbecher P, Geis C, Ringelstein M, Hartung HP, Friese MA, Kaufmann M, Malter MP, Madlener M, Thaler FS, Kümpfel T, Senel M, Häusler MG, Schneider H, Bergh FT, Kellinghaus C, Zettl UK, Wandinger KP, Melzer N, Gross CC, Lange P, Dreyhaupt J, Tumani H, Leypoldt F, Lewerenz J; German Network for Research on Autoimmune Encephalitis. CSF Findings in Acute NMDAR and LGI1 Antibody-Associated Autoimmune Encephalitis. Neurol Neuroimmunol Neuroinflamm. 2021 Oct 25;8(6):e1086.

Ringelstein M, Ayzenberg I, Lindenblatt G, Fischer K, Gahlen A, Novi G, Hayward-Könnecke H, Schippling S, Rommer PS, Kornek B, Zrzavy T, Biotti D, Ciron J, Audoin B, Berthele A, Giglhuber K, Zephir H, Kümpfel T, Berger R, Röther J, Häußler V, Stellmann JP, Whittam D, Jacob A, Kraemer M, Gueguen A, Deschamps R, Bayas A, Hümmert MW, Trebst C, Haarmann A, Jarius S, Wildemann B, Grothe M, Siebert N, Ruprecht K, Paul F, Collongues N, Marignier R, Levy M, Karenfort M, Deppe M, Albrecht P, Hellwig K, Gold R, Hartung HP, Meuth SG, Kleiter I, Aktas O; Neuromyelitis Optica Study Group (NEMOS). Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders. Neurol Neuroimmunol Neuroinflamm. 2021 Nov 16;9(1):e1100.

Marignier R, Hacohen Y, Cobo-Calvo A, Pröbstel AK, Aktas O, Alexopoulos H, Amato MP, Asgari N, Banwell B, Bennett J, Brilot F, Capobianco M, Chitnis T, Ciccarelli O, Deiva K, De Sèze J, Fujihara K, Jacob A, Kim HJ, Kleiter I, Lassmann H, Leite MI, Linington C, Meinl E, Palace J, Paul F, Petzold A, Pittock S, Reindl M, Sato DK, Selmaj K, Siva A, Stankoff B, Tintore M, Traboulsee A, Waters P, Waubant E, Weinshenker B, Derfuss T, Vukusic S, Hemmer B. Myelin-oligodendrocyte glycoprotein antibody-associated disease. Lancet Neurol. 2021 Sep;20(9):762-772.

Hiltensperger M, Beltrán E, Kant R, Tyystjärvi S, Lepennetier G, Domínguez Moreno H, Bauer IJ, Grassmann S, Jarosch S, Schober K, Buchholz VR, Kenet S, Gasperi C, Öllinger R, Rad R, Muschaweckh A, Sie C, Aly L, Knier B, Garg G, Afzali AM, Gerdes LA, Kümpfel T, Franzenburg S, Kawakami N, Hemmer B, Busch DH, Misgeld T, Dornmair K, Korn T. Skin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity. Nat Immunol. 2021 Jul;22(7):880-892.

Gaig C, Compta Y, Heidbreder A, Marti MJ, Titulaer MJ, Crijnen Y, Högl B, Lewerenz J, Erro ME, Garcia-Monco JC, Nigro P, Tambasco N, Patalong-Ogiewa M, Erdler M, Macher S, Berger-Sieczkowski E, Höftberger R, Geis C, Hutterer M, Milán-Tomás A, Martin-Bastida A, Lopez Manzanares L, Quintas S, Höglinger GU, Möhn N, Schoeberl F, Thaler FS, Asioli GM, Provini F, Plazzi G, Berganzo K, Blaabjerg M, Brüggemann N, Farias T, Ng CF, Giordana C, Herrero-San Martín A, Huebra L, Kotschet K, Liendl H, Montojo T, Morata C, Perez Perez J, Puertas I, Seifert-Held T, Seitz C, Mistieri Simabukuro M, Tellez N, Villacieros-Álvarez J, Willekens B, Sabater L, Iranzo A, Santamaria Cano J, Dalmau J, Graus F. Frequency and Characterization of Movement Disorders in Anti-IgLON5 Disease. Neurology. 2021 Aug 11;10.1212.

Gerhards R, Pfeffer LK, Lorenz J, Starost L, Nowack L, Thaler FS, Schlüter M, Rübsamen H, Macrini C, Winklmeier S, Mader S, Bronge M, Grönlund H, Feederle R, Hsia HE, Lichtenthaler SF, Merl-Pham J, Hauck SM, Kuhlmann T, Bauer IJ, Beltran E, Gerdes LA, Mezydlo A, Bar-Or A, Banwell B, Khademi M, Olsson T, Hohlfeld R, Lassmann H, Kümpfel T, Kawakami N, Meinl E. Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS. Acta Neuropathol Commun. 2020 Nov 30;8(1):207.

Specovius S, Zimmermann HG, Oertel FC, Chien C, Bereuter C, Cook LJ, Lana Peixoto MA, Fontenelle MA, Kim HJ, Hyun JW, Jung SK, Palace J, Roca-Fernandez A, Diaz AR, Leite MI, Sharma SM, Ashtari F, Kafieh R, Dehghani A, Pourazizi M, Pandit L, Dcunha A, Aktas O, Ringelstein M, Albrecht P, May E, Tongco C, Leocani L, Pisa M, Radaelli M, Martinez-Lapiscina EH, Stiebel-Kalish H, Hellmann M, Lotan I, Siritho S, de Seze J, Senger T, Havla J, Marignier R, Tilikete C, Cobo Calvo A, Bichuetti DB, Tavares IM, Asgari N, Soelberg K, Altintas A, Yildirim R, Tanriverdi U, Jacob A, Huda S, Rimler Z, Reid A, Mao-Draayer Y, de Castillo IS, Yeaman MR, Smith TJ, Brandt AU, Paul F; GJCF International Clinical Consortium for NMOSD. Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO). BMJ Open. 2020 Oct 29;10(10):e035397.

Jarius S, Pellkofer H, Siebert N, Korporal-Kuhnke M, Hümmert MW, Ringelstein M, Rommer PS, Ayzenberg I, Ruprecht K, Klotz L, Asgari N, Zrzavy T, Höftberger R, Tobia R, Buttmann M, Fechner K, Schanda K, Weber M, Asseyer S, Haas J, Lechner C, Kleiter I, Aktas O, Trebst C, Rostasy K, Reindl M, Kümpfel T, Paul F, Wildemann B; in cooperation with the Neuromyelitis Optica Study Group (NEMOS). Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 1: Results from 163 lumbar punctures in 100 adult patients. J Neuroinflammation. 2020 Sep 3;17(1):261.

Abrahamyan S, Eberspächer B, Hoshi MM, Aly L, Luessi F, Groppa S, Klotz L, Meuth SG, Schroeder C, Grüter T, Tackenberg B, Paul F, Then-Bergh F, Kümpfel T, Weber F, Stangel M, Bayas A, Wildemann B, Heesen C, Zettl U, Warnke C, Antony G, Hessler N, Wiendl H, Bittner S, Hemmer B, Gold R, Salmen A, Ruprecht K; German Competence Network Multiple Sclerosis (KKNMS); Other members of the KKNMS that acted as collaborators in this study. Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis. J Neurol Neurosurg Psychiatry. 2020 Jul;91(7):681-686.

Heitmann H, Haller B, Tiemann L, Mühlau M, Berthele A, Tölle TR, Salmen A, Ambrosius B, Bayas A, Asseyer S, Hartung HP, Heesen C, Stangel M, Wildemann B, Haars S, Groppa S, Luessi F, Kümpfel T, Nischwitz S, Meuth SG, Klotz L, Linker RA, Zettl UK, Ziemann U, Tumani H, Tackenberg B, Zipp F, Wiendl H, Gold R, Hemmer B, Ploner M. Longitudinal prevalence and determinants of pain in multiple sclerosis: results from the German National Multiple Sclerosis Cohort study. Pain. 2020 Apr;161(4):787-796.

Dietrich M, Koska V, Hecker C, Göttle P, Hilla AM, Heskamp A, Lepka K, Issberner A, Hallenberger A, Baksmeier C, Steckel J, Balk L, Knier B, Korn T, Havla J, Martínez-Lapiscina EH, Solà-Valls N, Manogaran P, Olbert ED, Schippling S, Cruz-Herranz A, Yiu H, Button J, Caldito NG, von Gall C, Mausberg AK, Stettner M, Zimmermann HG, Paul F, Brandt AU, Küry P, Goebels N, Aktas O, Berndt C, Saidha S, Green AJ, Calabresi PA, Fischer D, Hartung HP, Albrecht P. Protective effects of 4-aminopyridine in experimental optic neuritis and multiple sclerosis. Brain. 2020 Apr 1;143(4):1127-1142.

Gómez-Fernández P, Lopez de Lapuente Portilla A, Astobiza I, Mena J, Urtasun A, Altmann V, Matesanz F, Otaegui D, Urcelay E, Antigüedad A, Malhotra S, Montalban X, Castillo-Triviño T, Espino-Paisán L, Aktas O, Buttmann M, Chan A, Fontaine B, Gourraud PA, Hecker M, Hoffjan S, Kubisch C, Kümpfel T, Luessi F, Zettl UK, Zipp F, Alloza I, Comabella M, Lill CM, Vandenbroeck K. The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis. Cells. 2020 Jan 10;9(1):175.

Ringelstein M, Harmel J, Zimmermann H, Brandt AU, Paul F, Haarmann A, Buttmann M, Hümmert MW, Trebst C, Schroeder C, Ayzenberg I, Kleiter I, Hellwig K, Havla J, Kümpfel T, Jarius S, Wildemann B, Rommer P, Weber MS, Pellkofer H, Röpke L, Geis C, Retzlaff N, Zettl U, Deppe M, Klotz L, Young K, Stellmann JP, Kaste M, Kermer P, Marouf W, Lauda F, Tumani H, Graf J, Klistorner A, Hartung HP, Aktas O, Albrecht P; Neuromyelitis Optica Study Group (NEMOS). Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders. Neurology. 2020 Jan 28;94(4):e407-e418.

Nolan-Kenney RC, Liu M, Akhand O, Calabresi PA, Paul F, Petzold A, Balk L, Brandt AU, Martínez-Lapiscina EH, Saidha S, Villoslada P, Al-Hassan AA, Behbehani R, Frohman EM, Frohman T, Havla J, Hemmer B, Jiang H, Knier B, Korn T, Leocani L, Papadopoulou A, Pisa M, Zimmermann H, Galetta SL, Balcer LJ; International Multiple Sclerosis Visual System Consortium. Optimal intereye difference thresholds by optical coherence tomography in multiple sclerosis: An international study. Ann Neurol. 2019 May;85(5):618-629.

Johnen A, Bürkner PC, Landmeyer NC, Ambrosius B, Calabrese P, Motte J, Hessler N, Antony G, König IR, Klotz L, Hoshi MM, Aly L, Groppa S, Luessi F, Paul F, Tackenberg B, Bergh FT, Kümpfel T, Tumani H, Stangel M, Weber F, Bayas A, Wildemann B, Heesen C, Zettl UK, Zipp F, Hemmer B, Meuth SG, Gold R, Wiendl H, Salmen A; German Competence Network Multiple Sclerosis (KKNMS). Can we predict cognitive decline after initial diagnosis of multiple sclerosis? Results from the German National early MS cohort (KKNMS). J Neurol. 2019 Feb;266(2):386-397.

Graetz C, Gröger A, Luessi F, Salmen A, Zöller D, Schultz J, Siller N, Fleischer V, Bellenberg B, Berthele A, Biberacher V, Havla J, Hecker M, Hohlfeld R, Infante-Duarte C, Kirschke JS, Kümpfel T, Linker R, Paul F, Pfeuffer S, Sämann P, Toenges G, Weber F, Zettl UK, Jahn-Eimermacher A, Antony G, Groppa S, Wiendl H, Hemmer B, Mühlau M, Lukas C, Gold R, Lill CM, Zipp F. Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis. Mult Scler. 2019 Apr;25(5):661-668.

Bittner S, Engel S, Lange C, Weber MS, Haghikia A, Luessi F, Korn T, Klotz L, Bayas A, Paul F, Heesen C, Stangel M, Wildemann B, Bergh FT, Tackenberg B, Trebst C, Warnke C, Linker R, Kerschensteiner M, Zettl U, Tumani H, Brück W, Meuth SG, Kümpfel T, Hemmer B, Wiendl H, Gold R, Zipp F. Diagnostik und Therapie von Tuberkulose unter Immuntherapien für Multiple Sklerose : Aktueller Stand und Empfehlungen in Deutschland [Diagnostics and treatment of tuberculosis under immunotherapy for multiple sclerosis : Current status and recommendations in Germany]. Nervenarzt. 2019 Dec;90(12):1245-125

Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Hellwig K, Pache F, Ruprecht K, Havla J, Kümpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Krumbholz M, Zeltner L, Ziemann U, Linker R, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Zettl UK, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C; NEMOS (Neuromyelitis Optica Study Group). Apheresis therapies for NMOSD attacks: A retrospective study of 207 therapeutic interventions. Neurol Neuroimmunol Neuroinflamm. 2018 Sep 26;5(6):e504.

Stellmann JP, Krumbholz M, Friede T, Gahlen A, Borisow N, Fischer K, Hellwig K, Pache F, Ruprecht K, Havla J, Kümpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Young KL, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker RA, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Zettl U, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C, Kleiter I; NEMOS (Neuromyelitis Optica Study Group). Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response. J Neurol Neurosurg Psychiatry. 2017 Aug;88(8):639-647.

Borisow N, Kleiter I, Gahlen A, Fischer K, Wernecke KD, Pache F, Ruprecht K, Havla J, Krumbholz M, Kümpfel T, Aktas O, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Weissert R, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker RA, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Winkelmann A, Marouf W, Rückriem L, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C, Hellwig K; NEMOS (Neuromyelitis Optica Study Group). Influence of female sex and fertile age on neuromyelitis optica spectrum disorders. Mult Scler. 2017 Jul;23(8):1092-1103.

Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Wegner B, Hellwig K, Pache F, Ruprecht K, Havla J, Krumbholz M, Kümpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker R, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Winkelmann A, Marouf W, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C; Neuromyelitis Optica Study Group. Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016 Feb;79(2):206-16.

Diem R, Molnar F, Beisse F, Gross N, Drüschler K, Heinrich SP, Joachimsen L, Rauer S, Pielen A, Sühs KW, Linker RA, Huchzermeyer C, Albrecht P, Hassenstein A, Aktas O, Guthoff T, Tonagel F, Kernstock C, Hartmann K, Kümpfel T, Hein K, van Oterendorp C, Grotejohann B, Ihorst G, Maurer J, Müller M, Volkmann M, Wildemann B, Platten M, Wick W, Heesen C, Schiefer U, Wolf S, Lagrèze WA. Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol. BMJ Open. 2016 Mar 1;6(3):e010956.

Sadovnick AD, Traboulsee AL, Bernales CQ, Ross JP, Forwell AL, Yee IM, Guillot-Noel L, Fontaine B, Cournu-Rebeix I, Alcina A, Fedetz M, Izquierdo G, Matesanz F, Hilven K, Dubois B, Goris A, Astobiza I, Alloza I, Antigüedad A, Vandenbroeck K, Akkad DA, Aktas O, Blaschke P, Buttmann M, Chan A, Epplen JT, Gerdes LA, Kroner A, Kubisch C, Kümpfel T, Lohse P, Rieckmann P, Zettl UK, Zipp F, Bertram L, Lill CM, Fernandez O, Urbaneja P, Leyva L, Alvarez-Cermeño JC, Arroyo R, Garagorri AM, García-Martínez A, Villar LM, Urcelay E, Malhotra S, Montalban X, Comabella M, Berger T, Fazekas F, Reindl M, Schmied MC, Zimprich A, Vilariño-Güell C. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients. G3 (Bethesda). 2016 Jul 7;6(7):2073-9.

Andlauer TF, Buck D, Antony G, Bayas A, Bechmann L, Berthele A, Chan A, Gasperi C, Gold R, Graetz C, Haas J, Hecker M, Infante-Duarte C, Knop M, Kümpfel T, Limmroth V, Linker RA, Loleit V, Luessi F, Meuth SG, Mühlau M, Nischwitz S, Paul F, Pütz M, Ruck T, Salmen A, Stangel M, Stellmann JP, Stürner KH, Tackenberg B, Then Bergh F, Tumani H, Warnke C, Weber F, Wiendl H, Wildemann B, Zettl UK, Ziemann U, Zipp F, Arloth J, Weber P, Radivojkov-Blagojevic M, Scheinhardt MO, Dankowski T, Bettecken T, Lichtner P, Czamara D, Carrillo-Roa T, Binder EB, Berger K, Bertram L, Franke A, Gieger C, Herms S, Homuth G, Ising M, Jöckel KH, Kacprowski T, Kloiber S, Laudes M, Lieb W, Lill CM, Lucae S, Meitinger T, Moebus S, Müller-Nurasyid M, Nöthen MM, Petersmann A, Rawal R, Schminke U, Strauch K, Völzke H, Waldenberger M, Wellmann J, Porcu E, Mulas A, Pitzalis M, Sidore C, Zara I, Cucca F, Zoledziewska M, Ziegler A, Hemmer B, Müller-Myhsok B. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation. Sci Adv. 2016 Jun 17;2(6):e1501678.

Kuhle J, Hardmeier M, Disanto G, Gugleta K, Ecsedi M, Lienert C, Amato MP, Baum K, Buttmann M, Bayas A, Brassat D, Brochet B, Confavreux C, Edan G, Färkkilä M, Fredrikson S, Frontoni M, D'Hooghe M, Hutchinson M, De Keyser J, Kieseier BC, Kümpfel T, Rio J, Polman C, Roullet E, Stolz C, Vass K, Wandinger KP, Kappos L; European Long-term Follow-up Study Group in Interferon β-1b in Secondary-progressive Multiple Sclerosis. A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis. Mult Scler. 2016 Apr;22(4):533-43.

Klotz L, Berthele A, Brück W, Chan A, Flachenecker P, Gold R, Haghikia A, Hellwig K, Hemmer B, Hohlfeld R, Korn T, Kümpfel T, Lang M, Limmroth V, Linker RA, Meier U, Meuth SG, Paul F, Salmen A, Stangel M, Tackenberg B, Tumani H, Warnke C, Weber MS, Ziemssen T, Zipp F, Wiendl H. Monitoring von Blutparametern unter verlaufsmodifizierender MS-Therapie : Substanzspezifische Relevanz und aktuelle Handlungsempfehlungen [Monitoring of blood parameters under course-modified MS therapy : Substance-specific relevance and current recommendations for action]. Nervenarzt. 2016 Jun;87(6):645-59.

Dankowski T, Buck D, Andlauer TF, Antony G, Bayas A, Bechmann L, Berthele A, Bettecken T, Chan A, Franke A, Gold R, Graetz C, Haas J, Hecker M, Herms S, Infante-Duarte C, Jöckel KH, Kieseier BC, Knier B, Knop M, Kümpfel T, Lichtner P, Lieb W, Lill CM, Limmroth V, Linker RA, Loleit V, Meuth SG, Moebus S, Müller-Myhsok B, Nischwitz S, Nöthen MM, Paul F, Pütz M, Ruck T, Salmen A, Stangel M, Stellmann JP, Strauch K, Stürner KH, Tackenberg B, Then Bergh F, Tumani H, Waldenberger M, Weber F, Wiendl H, Wildemann B, Zettl UK, Ziemann U, Zipp F, Hemmer B, Ziegler A; German Competence Network for Multiple Sclerosis (KKNMS). Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array. Genet Epidemiol. 2015 Dec;39(8):601-8.

Lill CM, Luessi F, Alcina A, Sokolova EA, Ugidos N, de la Hera B, Guillot-Noël L, Malhotra S, Reinthaler E, Schjeide BM, Mescheriakova JY, Mashychev A, Wohlers I, Akkad DA, Aktas O, Alloza I, Antigüedad A, Arroyo R, Astobiza I, Blaschke P, Boyko AN, Buttmann M, Chan A, Dörner T, Epplen JT, Favorova OO, Fedetz M, Fernández O, García-Martínez A, Gerdes LA, Graetz C, Hartung HP, Hoffjan S, Izquierdo G, Korobko DS, Kroner A, Kubisch C, Kümpfel T, Leyva L, Lohse P, Malkova NA, Montalban X, Popova EV, Rieckmann P, Rozhdestvenskii AS, Schmied C, Smagina IV, Tsareva EY, Winkelmann A, Zettl UK, Binder H, Cournu-Rebeix I, Hintzen R, Zimprich A, Comabella M, Fontaine B, Urcelay E, Vandenbroeck K, Filipenko M, Matesanz F, Zipp F, Bertram L. Genome-wide significant association with seven novel multiple sclerosis risk loci. J Med Genet. 2015 Dec;52(12):848-55.

Publications

MS discordant monozygotic twins help to untangle environmental and genetic influences in immune profiles

PET imaging can improve montoring of Natalizumab-associated PML

Secret, highly active life of nerve cell contacts in the brain revealed

Details of target-recognition by autoantibodies to myelin oligodendrocyte glycoprotein uncovered

Synaptic FUS(S) at the heart of neuronal dysfunction in ALS/FTD

An encephalitogenic autoantibody cross-reacts to a tumor antigen

Immune cells remove synapses in the inflamed gray matter

Resurrection of a pathogenic immune response from a historical case

Single cell ablation reveals the rules of myelin replacement

Twin effect overrides disease specific immune signatures

Neuronal activity controls circuit formation following spinal cord injury

Detection of early adaptive immune activation in prodromal MS

Circulating autoreactive B cells specific for GAD65

Leaky membranes promote axon degeneration in MS model

DNA methylation signatures are associated with MS phenotype

Pathogenic mechanisms of patient antibodies recognizing MOG

Shifty phagocytes track the fate of neuroinflammatory lesions

What´s it got to do with our guts? A possible link between the gut microbiome and MS!

Novel biomarkers for a subset of brain tumors

Early stages of myelin injury revealed by ultrastructural and dynamic analysis

Widespread synapse loss in multiple sclerosis gray matter

New immunoregulation and biomarker

FGF22 regulates circuit formation following spinal cord injury

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