Ralf Linker

Publications of Ralf Linker

• Report on the 3'rd scientific meeting of the "Verein zur Förderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Nov. 4'th - Nov. 6'th, 2011.

  Authors: Christoph Kleinschnitz, Sven G Meuth, Tim Magnus, Thomas Korn, Ralf A Linker

  Experimental & translational stroke medicine. 02/2012; 4(1):2.

  ABSTRACT: From November 4th- 6th 2011, the 3rd NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. Like in the previous years, the meeting provided an excellent platform for scientificABSTRACT: From November 4th- 6th 2011, the 3rd NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. Like in the previous years, the meeting provided an excellent platform for scientific exchange and the presentation of innovative projects for young colleagues in the fields of neurovascular research, neuroinflammation and neurodegeneration. As kick-off to the scientific sessions, Reinhard Hohlfeld, Head of the Institute for Clinical Neuroimmunology in Munich, gave an illustrious overview on the many fascinations of neuroimmunologic research. A particular highlight on the second day of the meeting was the award of the 1'st NEUROWIND e.V. prize for young academics in the field of experimental neurology. This award is posted for young colleagues under the age of 35 with a significant achievement in the field of neurovascular research, neuroinflammation or neurodegeneration and comprises an amount of 20.000 Euro, founded by Merck Serono GmbH, Darmstadt. Germany. The first prize was awarded to Ivana Nikic from Martin Kerschensteiner's group in Munich for her brilliant work on a reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis, published in Nature Medicine in 2011. This first prize award ceremony was a great incentive for the next call for proposals now upcoming in 2012.

• Aquaporin 4 antibody positive central nervous system autoimmunity and multiple sclerosis are characterized by a distinct profile of antibodies to herpes viruses.

  Authors: Johann Sellner, Sabine Cepok, Sudhakar Reddy Kalluri, Axel Nestler, Ingo Kleiter, Tania Kümpfel, Ralf Linker, Arthur Melms, Til Menge, Hayrettin Tumani, Friedemann Paul, Bernhard Hemmer, Achim Berthele

  Neurochemistry international. 11/2010; 57(6):662-7.

  Viral infections are implicated in the onset and promotion of autoimmunity in genetically predisposed individuals. In this study, immune response patterns to herpes viruses were compared in aquaporinViral infections are implicated in the onset and promotion of autoimmunity in genetically predisposed individuals. In this study, immune response patterns to herpes viruses were compared in aquaporin 4 (AQP4) antibody positive central nervous system (CNS) autoimmunity and multiple sclerosis (MS). Serum samples of patients with AQP4 antibody positive CNS autoimmunity (n=52), relapsing-remitting MS (n=55) and controls including non-autoimmune neurological disorders and healthy individuals (n=56) were tested for IgG antibodies to herpes viruses 1-6 (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6) using commercial ELISA kits. AQP4 antibody positive CNS autoimmunity cases most frequently had IgG responses to four viruses (38.5%), while presence of antibodies to three herpes viruses was most common in MS and controls (41.8% and 35.7%, respectively). Compared to MS, AQP4 positive cases had a significantly higher CMV seropositivity rate (P=0.003) and a lower prevalence of EBV antibodies (P=0.01). The analysis of immunoreactivity of samples above the diagnostic threshold revealed that in AQP4 positive CNS autoimmunity the IgG response to EBV (P<0.001) and VZV (P<0.01) was lower than in MS, whereas immununoreactivity to HSV-1 was higher than in controls (P<0.01). The distinct pattern of seroprevalence and immunoreactivity against herpes viruses in AQP4 positive CNS autoimmunity and MS provide further insights to the pathogenetical heterogeneity. Whether these findings reflect an epi-phenomenon of autoimmune disorders or indicate a disease-specific deregulated virus-host interaction needs to be examined in further studies.

• Report on the 1st scientific meeting of the "Verein zur Förderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Mittenwalde/Motzen, Germany, Oct. 30th - Nov. 1st, 2009.

  Authors: Tim Magnus, Ralf Linker, Sven G Meuth, Christoph Kleinschnitz, Thomas Korn

  Experimental & translational stroke medicine. 03/2010; 2:7.

  Report on the 1st scientific meeting of the "Verein zur Forderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Mittenwalde/Motzen, Germany, Oct. 30th - Nov. 1st,Report on the 1st scientific meeting of the "Verein zur Forderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Mittenwalde/Motzen, Germany, Oct. 30th - Nov. 1st, 2009. A scientific meeting report.

• Temporal pattern of ICAM-I mediated regulatory T cell recruitment to sites of inflammation in adoptive transfer model of multiple sclerosis.

  Authors: Sebastian Doerck, Kerstin Göbel, Gesa Weise, Tilman Schneider-Hohendorf, Michael Reinhardt, Peter Hauff, Nicholas Schwab, Ralf Linker, Mathias Mäurer, Sven G Meuth, Heinz Wiendl

  PloS one. 01/2010; 5(11):e15478.

  Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmuneMigration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3) only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development.

• Function of neurotrophic factors beyond the nervous system: inflammation and autoimmune demyelination.

  Authors: Ralf Linker, Ralf Gold, Fred Luhder

  Critical reviews in immunology. 02/2009; 29(1):43-68.

  In the nervous system, neurotrophic factors play a role during development, especially for the differentiation of neuronal and glial cells. Moreover, they promote cell survival of neurons, axons, andIn the nervous system, neurotrophic factors play a role during development, especially for the differentiation of neuronal and glial cells. Moreover, they promote cell survival of neurons, axons, and oligodendrocytes, as well as their precursors, in vitro and in lesional paradigms. In recent years, several functions of neurotrophic factors outside the nervous system have been described, with a special focus on the immune system as well as on models of autoimmune demyelination, such as experimental autoimmune encephalomyelitis (EAE). In the family of neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were investigated. NGF may influence B-cell as well as T-cell function and particularly plays a role in macrophage migration into inflamed lesions. BDNF is produced by several immune-cell subtypes in vitro and also in multiple sclerosis (MS) plaques. This observation gave rise to the concept of neuroprotective autoimmunity, implying that immune-cell infiltration in the nervous system may not only be detrimental but may also play a beneficial role, for example, through the production of neurotrophic factors. In the family of neurotrophic cytokines, ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) share some common protective roles in axons and oligodendrocytes. In EAE, endogenous CNTF targets myelin, oligodendroglial cells, and axons. In contrast, LIF exerts protective functions on oligodendrocytes in some models but is also able to interact with the immune response and may modulate T-cell, monocyte and neutrophil functions. In summary, neurotrophic factors have distinct roles in the immune system during autoimmunity and may modulate immune responses as well as the susceptibility of the target tissue.

• Rescue therapy with anti-CD20 treatment in neuroimmunologic breakthrough disease.

  Authors: Andrew Chan, De-Hyung Lee, Ralf Linker, Alexander Mohr, Klaus V Toyka, Ralf Gold

  Journal of neurology. 12/2007; 254(11):1604-6.

• Association of a null mutation in the CNTF gene with early onset of multiple sclerosis.

  Authors: Ralf Giess, Mathias Mäurer, Ralf Linker, Ralf Gold, Monika Warmuth-Metz, Klaus V Toyka, Michael Sendtner, Peter Rieckmann

  Archives of neurology. 04/2002; 59(3):407-9.

  BACKGROUND: Immune-mediated demyelination and axonal damage lead to early functional impairment in multiple sclerosis (MS). Ciliary neurotrophic factor (CNTF) is a potent survival factor for neuronsBACKGROUND: Immune-mediated demyelination and axonal damage lead to early functional impairment in multiple sclerosis (MS). Ciliary neurotrophic factor (CNTF) is a potent survival factor for neurons and oligodendrocytes and may be relevant in reducing tissue destruction during inflammatory attacks. SUBJECTS AND METHODS: We screened 288 unselected patients with multiple sclerosis (MS) (mean age, 40.2 +/- 10.2 years; range, 18-71 years) for a previously described homozygous null mutation within the CNTF gene leading to a truncated, biologically inactive protein. The G-to-A CNTF null mutation at position -6 of the second exon was identified by a HaeIII polymorphism of the polymerase chain reaction-amplified genomic DNA. RESULTS: The homozygous CNTF null mutation (CNTF -/-) was found in 7 (2.4%) of the 288 randomly selected patients with MS. Patients with the CNTF -/- genotype had a significantly earlier onset of disease (17 vs 27 years; Mann-Whitney test, P =.007) with predominant motor symptoms. CONCLUSIONS: These results suggest that CNTF contributes to time and site of early clinical manifestation. The frequency of patients with MS with a homozygous CNTF null mutation in this population was not higher than in control groups, indicating that the CNTF null mutation is not a risk factor for development of MS.