Our aims
We are interested in the immunopathogenesis of multiple sclerosis (MS) and related diseases.
Inflammatory diseases of the CNS comprise a spectrum of disorders amongst which Multiple Sclerosis (MS) is the most frequent one. These diseases are due to misguided autoreactive immune cells that attack the own nervous system and induce chronic inflammation. The identification of autoantibodies in a subset of patients lead to the recognition of new disease entities, neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-associated disorders (MOGAD) that overlap with MS; for most patients, however, the target of their autoimmune response is still unknown. The stratification of patients based on the autoimmune target they recognize, has a great impact on our concepts of pathogenesis and is important for optimizing therapy.
We aim to (1) explore the autoimmunity against known target antigens and identify novel targets of autoimmune responses to stratify patients, (2) study the complex microenvironment in MS lesions that fosters persistence of B cells, (3) recognize mechanisms of actions of immunomodulatory drugs applied to patients with MS and related disorders.
Our approaches
We determine brain-reactive antibodies (Abs) using immunostaining, transfected cells and ELISA. For functional characterization and identification of new targets, we apply mass-spectrometry and recombinant Abs obtained from single-cell sorting. Autoreactive human immune cells are analysed by in vitro culture systems.
We examine blood and spinal fluid samples from patients to monitor the individual treatment response using flow cytometry, quantitative PCR and single-cell transcriptomics. Our cell culture systems with glial cells and immune cells are used to study mechanisms of disease modifying drugs in vitro.
Our research is performed in close collaboration with the associated Junior group of Simone Mader (Junior group Mader) and the clinical group of our institute.
Ongoing projects
Autoimmunity to known targets in the CNS
One focus of our work is the autoimmunity against myelin oligodendrocyte glycoprotein (MOG). We have identified epitopes on the extracellular part of MOG recognized by autoantibodies from patients with MOGAD. To understand features of MOG required for autoantibody binding, we use variants of MOG displayed on transfected cells, lipid-coated beads and correctly folded recombinant MOG.
We found that MOG-Abs from patients are pathogenic in transfer experiments to rats via two mechanisms, demyelination and enhancement of cognate T cell activation (in collaboration with N Kawakami). Now we analyse the contribution of different FcR effector mechanisms to these pathomechanisms of MOG-Abs.
We are using in vitro differentiation of B cells to antibody secreting cells, EBV transformation and single cell analysis to get insight into autoreactive B.
Strategy to analyse pathogenicity of patient-derived MOG-IgG.
Blood was drawn from patients with Abs to human MOG that cross-react with rodent MOG. MOG-IgG were affinity purified and transferred into rats with experimental autoimmune encephalomyelitis, where they enhanced disorder by two different mechanisms. Together with MBP-specific T cells that strongly breach the blood-brain barrier, the MOG-Abs induced demyelination (LFB staining) with deposition of terminal complement complex similar to the disorder seen in some patients with MOG-Abs. Second, together with cognate MOG-specific T cells, MOG-IgG (compared with control-IgG) enhanced T-cell infiltration. Cartoon from the review Mader et al. Curr. Opin. Neurol. 2020. Original paper: Spadaro et al. Ann Neurol. 2018.
Identification of novel autoimmune targets
Previously, we have identified neurofascin as target of an autoimmune response. Autoantibodies to neurofascin are now commonly used to stratify patients with inflammation in the peripheral nervous system. Recently, we have detected autoantibodies to oligodendrocyte myelin glycoprotein (OMGP) in some patients and found in an animal model (in collaboration with Naoto Kawakami) that T cells specific for OMGP mediate cortical encephalitis. Now we analyse the clinical spectrum of patients with autoimmunity to OMGP. Furthermore, we also identified, with immunostainings, subjects who have brain-reactive Abs. Now we aim to identify their molecular targets.
Regulation of B cell survival via the BAFF-APRIL system
The survival of B cells is regulated by the cytokines BAFF and APRIL. Previously, we detected that human astrocytes produce BAFF and that in MS lesions, BAFF is as highly expressed as in lymphatic tissue. We found that the survival of B cells is regulated by shedding of the BAFF-APRIL receptors TACI and BCMA and uncovered together with Stefan Lichtenthaler (DZNE) the proteases that are mediating this shedding. Our finding that γ-secretase sheds BCMA from plasma cells might be used to improve BCMA-targeted immunotherapy for multiple myeloma. We aim to detect further features of the BAFF-APRIL system and analyse its utility as biomarker.
The survival receptors BCMA and TACI are shed from B cells.
Left: BCMA is constitutively shed by the intramembranous enzyme g-secretase, the released sBCMA functions as decoy for APRIL and depending on its oligomerization also for BAFF.
Right: TACI is shed by ADAM10 or ADAM17 adjacent to the membrane. The released sTACI is a decoy for APRIL and BAFF, the membrane stub is degraded by the g-secretase. Both sBCMA and sTACI serve as biomarkers for B cell contribution in autoimmunity and as tumor markers in certain malignancies. Cartoon modified from the review Meinl et al. Trends Immunol. 2018. Original paper: Laurent et al. Nat commun. 2015; Hoffmann et al. J.Immunol. 2015. Thaler et al. Neuro Oncol. 2017.
Mechanisms of action of drugs used to treat patients with MS and related disorders
This is a long-standing interest of our lab. Previous work examined IFN-β, Glatiramer acetate, Natalizumab, Rituximab and Fingolimod. Currently, we are investigating the effects of BTK-inhibitors, anti-CD19, anti-CD20 and Cladribine using ex-vivo analysis of immune cells from treated patients and in vitro systems. This is done in close collaboration with our outpatient clinic.
Immune response to SARS-CoV-2
We are applying our experience with human B cells to analyse the immunity to SARS-CoV-2. We have found that SARS-CoV-2 specific memory B cells persist in the blood of COVID-19 patients for a long time, even when no specific IgG is detectable in the blood anymore. These persisting memory B cells can give rise to functional antibodies that neutralize SARS-CoV-2. This finding is of critical importance to the question of long-term immunity, as memory B cells can rapidly differentiate into antibody-producing cells upon re-infection (or infection after vaccination) and evolve to better bind viral variants. We now analyse the effects of immunosuppressive treatments on the development and persistence of SARS-CoV-2 specific memory B cells after vaccination.
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Publication highlights of recent years (since 2015)
Ho S, Oswald E, Wong HK, Vural A, Yilmaz V, Tüzün E, Türkoğlu R, Straub T, Meinl I, Thaler F, Kümpfel T, Meinl E*, Mader S*.(2023) Ocrelizumab Treatment Modulates B-Cell Regulating Factors in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 10(2):e200083.
Fichtner, M. L., Rübsamen, H., Smolle, M., Schaller, J., Feederle, R., Bültmann, A., Kümpfel, T., Schneider, P., Thaler, F. S., & Meinl, E. (2023). Features of Isoforms of Human Soluble TACI. Journal Immunol (Baltimore, Md. : 1950), 211(2), 199–208.
Mader S, Ho S, Wong HK, Baier S, Winklmeier S, Riemer C, Rübsamen H, Fernandez IM, Gerhards R, Du C, Chuquisana O, Lünemann JD, Lux A, Nimmerjahn F, Bradl M*, Kawakami N*, Meinl E*. Dissection of complement and Fc-receptor-mediated pathomechanisms of autoantibodies to myelin oligodendrocyte glycoprotein. Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2300648120.
Ho S, Oswald E, Wong HK, Vural A, Yilmaz V, Tüzün E, Türkoğlu R, Straub T, Meinl I, Thaler F, Kümpfel T, Meinl E, Mader S. Ocrelizumab Treatment Modulates B-Cell Regulating Factors in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2023 Jan 26;10(2):e200083.
Winklmeier S, Eisenhut K, Taskin D, Rübsamen H, Gerhards R, Schneider C, Wratil PR, Stern M, Eichhorn P, Keppler OT, Klein M, Mader S, Kümpfel T, Meinl E. Persistence of functional memory B cells recognizing SARS-CoV-2 variants despite loss of specific IgG. iScience. 2022 Jan 21;25(1):103659. doi: 10.1016/j.isci.2021.103659.
Schlüter M, Oswald E, Winklmeier S, Meinl I, Havla J, Eichhorn P, Meinl E*, Kümpfel T*.Effects of Natalizumab Therapy on Intrathecal Immunoglobulin G Production Indicate Targeting of Plasmablasts. Neurol Neuroimmunol Neuroinflamm. 2021 Jul 1;8(5):e1030.(* co-senior author)
Macrini C, Gerhards R, Winklmeier S, Bergmann L, Mader S, Spadaro M, Vural A, Smolle M, Hohlfeld R, Kümpfel T, Lichtenthaler S, Franquelim H, Jenne D, Meinl E. Features of MOG required for recognition by patients with MOG-antibody-associated disorders. Brain, 2021, 144(8):2375-2389.
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.
Winklmeier S, Schlüter M, Spadaro M, Thaler FS, Vural A, Gerhards R, Macrini C, Mader S, Kurne A, Inan B, Karabudak R, Özbay FG, Esendagli G, Hohlfeld R, Kümpfel T, Meinl E. Identification of circulating MOG-specific B cells in patients with MOG antibodies. Neurol Neuroimmunol Neuroinflamm. 2019 Oct 14;6(6):625. Erratum in: Neurol Neuroimmunol Neuroinflamm. 2019 Nov 15;7(1).
Thaler FS, Thaller AL, Biljecki M, Schuh E, Winklmeier S, Mahler CF, Gerhards R, Völk S, Schnorfeil F, Subklewe M, Hohlfeld R, Kümpfel T, Meinl E. Abundant glutamic acid decarboxylase (GAD)-reactive B cells in gad-antibody-associated neurological disorders. Ann Neurol. 2019 Mar;85(3):448-454.
Spadaro M, Winklmeier S, Beltrán E, Macrini C, Höftberger R, Schuh E, Thaler FS, Gerdes LA, Laurent S, Gerhards R, Brändle S, Dornmair K, Breithaupt C, Krumbholz M, Moser M, Krishnamoorthy G, Kamp F, Jenne D, Hohlfeld R, Kümpfel T, Lassmann H, Kawakami N, Meinl E. Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein. Ann Neurol. 2018 Aug;84(2):315-328.
Thaler FS, Laurent SA, Huber M, Mulazzani M, Dreyling M, Ködel U, Kümpfel T, Straube A, Meinl E, von Baumgarten L. Soluble TACI and soluble BCMA as biomarkers in primary central nervous system lymphoma. Neuro Oncol. 2017 Nov 29;19(12):1618-1627.
Schuh E, Musumeci A, Thaler FS, Laurent S, Ellwart JW, Hohlfeld R, Krug A, Meinl E. Human Plasmacytoid Dendritic Cells Display and Shed B Cell Maturation Antigen upon TLR Engagement. J Immunol. 2017 Apr 15;198(8):3081-3088.
Spadaro M, Gerdes LA, Krumbholz M, Ertl-Wagner B, Thaler FS, Schuh E, Metz I, Blaschek A, Dick A, Brück W, Hohlfeld R, Meinl E*, Kümpfel T. Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2016 Jun 30;3(5):e257. (* co-senior author)
Schuh E, Berer K, Mulazzani M, Feil K, Meinl I, Lahm H, Krane M, Lange R, Pfannes K, Subklewe M, Gürkov R, Bradl M, Hohlfeld R, Kümpfel T, Meinl E*, Krumbholz M. Features of Human CD3+CD20+ T Cells. J Immunol. 2016 Aug 15;197(4):1111-7. (* co-senior author)
Hoffmann FS, Hofereiter J, Rübsamen H, Melms J, Schwarz S, Faber H, Weber P, Pütz B, Loleit V, Weber F, Hohlfeld R, Meinl E*, Krumbholz M. Fingolimod induces neuroprotective factors in human astrocytes. J Neuroinflammation. 2015 Sep 30;12:184. (* co-senior author)
Laurent SA, Hoffmann FS, Kuhn PH, Cheng Q, Chu Y, Schmidt-Supprian M, Hauck SM, Schuh E, Krumbholz M, Rübsamen H, Wanngren J, Khademi M, Olsson T, Alexander T, Hiepe F, Pfister HW, Weber F, Jenne D, Wekerle H, Hohlfeld R, Lichtenthaler SF, Meinl E. γ-Secretase directly sheds the survival receptor BCMA from plasma cells. Nat Commun. 2015 Jun 11;6:7333.
Spadaro M, Gerdes LA, Mayer MC, Ertl-Wagner B, Laurent S, Krumbholz M, Breithaupt C, Högen T, Straube A, Giese A, Hohlfeld R, Lassmann H, Meinl E*, Kümpfel T. Histopathology and clinical course of MOG-antibody-associated encephalomyelitis. Ann Clin Transl Neurol. 2015 Mar;2(3):295-301. (* co-senior author)
Hoffmann FS, Kuhn PH, Laurent SA, Hauck SM, Berer K, Wendlinger SA, Krumbholz M, Khademi M, Olsson T, Dreyling M, Pfister HW, Alexander T, Hiepe F, Kümpfel T, Crawford HC, Wekerle H, Hohlfeld R, Lichtenthaler SF, Meinl E. The immunoregulator soluble TACI is released by ADAM10 and reflects B cell activation in autoimmunity. J Immunol. 2015 Jan 15;194(2):542-52.
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Teschner VE, Fleck AK, Walter C, Schwarze AS, Eschborn M, Wirth T, Steinberg OV, Schulte-Mecklenbeck A, Lu IN, Herrera-Rivero M, Janoschka C, Lünemann JD, Schwab N, Meyer Zu Hörste G, Varghese J, Gross CC, Pul R, Kleinschnitz C, Mader S, Meinl E, Stoll M, Wiendl H, Klotz L. (2023) Single-cell profiling reveals preferential reduction of memory B cell subsets in cladribine patients that correlates with treatment response. Ther Adv Neurol Disord. 16:17562864231211077.
Boldrini, V. O., Mader, S., Kümpfel, T., & Meinl, E. (2023). Ublituximab: A new FDA-approved anti-CD20 mAb for relapsing forms of multiple sclerosis. Mult scler relat disord, 75, 104733.
Engels, D., Mader, S., Förderreuther, S., Reindl, M., Havla, J., Meinl, E., Kümpfel, T., & Gerdes, L. A. (2023). MOG-IgG-Associated Bilateral Optic Neuritis in Temporal Relation to Monkeypox Vaccination. Ann neurol, 93(6), 1216–1217.
Fichtner, M. L., Rübsamen, H., Smolle, M., Schaller, J., Feederle, R., Bültmann, A., Kümpfel, T., Schneider, P., Thaler, F. S., & Meinl, E. (2023). Features of Isoforms of Human Soluble TACI. Journal Immunol (Baltimore, Md. : 1950), 211(2), 199–208.
Mader S, Ho S, Wong HK, Baier S, Winklmeier S, Riemer C, Rübsamen H, Fernandez IM, Gerhards R, Du C, Chuquisana O, Lünemann JD, Lux A, Nimmerjahn F, Bradl M*, Kawakami N*, Meinl E*. Dissection of complement and Fc-receptor-mediated pathomechanisms of autoantibodies to myelin oligodendrocyte glycoprotein. Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2300648120.
Biljecki M, Eisenhut K, Beltrán E, Winklmeier S, Mader S, Thaller A, Eichhorn P, Steininger P, Flierl-Hecht A, Lewerenz J, Kümpfel T, Kerschensteiner M, Meinl E, Thaler FS. Antibodies Against Glutamic Acid Decarboxylase 65 Are Locally Produced in the CSF and Arise During Affinity Maturation. Neurol Neuroimmunol Neuroinflamm. 2023 Feb 23;10(3):e200090.
Ho S, Oswald E, Wong HK, Vural A, Yilmaz V, Tüzün E, Türkoğlu R, Straub T, Meinl I, Thaler F, Kümpfel T, Meinl E, Mader S. Ocrelizumab Treatment Modulates B-Cell Regulating Factors in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2023 Jan 26;10(2):e200083.
Spatola M, Chuquisana O, Jung W, Lopez JA, Wendel EM, Ramanathan S, Keller CW, Hahn T, Meinl E, Reindl M, Dale RC, Wiendl H, Lauffenburger DA, Rostásy K, Brilot F, Alter G, Lünemann JD. Humoral signatures of MOG-antibody-associated disease track with age and disease activity. Cell Rep Med. 2023 Feb 21;4(2):100913
Appeltshauser L, Junghof H, Messinger J, Linke J, Haarmann A, Ayzenberg I, Baka P, Dorst J, Fisse AL, Grüter T, Hauschildt V, Jörk A, Leypoldt F, Mäurer M, Meinl E, Michels S, Motte J, Pitarokoili K, Stettner M, Villmann C, Weihrauch M, Welte GS, Zerr I, Heinze KG, Sommer C, Doppler K. Anti-pan-neurofascin antibodies induce subclass-related complement activation and nodo-paranodal damage. Brain. 2022 Nov 8:awac418.
Preisendörfer S, Ishikawa Y, Hennen E, Winklmeier S, Schupp JC, Knüppel L, Fernandez IE, Binzenhöfer L, Flatley A, Juan-Guardela BM, Ruppert C, Guenther A, Frankenberger M, Hatz RA, Kneidinger N, Behr J, Feederle R, Schepers A, Hilgendorff A, Kaminski N, Meinl E, Bächinger HP, Eickelberg O, Staab-Weijnitz CA. FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis. Cells. 2022 Apr 14;11(8):1341.
Winklmeier S, Eisenhut K, Taskin D, Rübsamen H, Gerhards R, Schneider C, Wratil PR, Stern M, Eichhorn P, Keppler OT, Klein M, Mader S, Kümpfel T, Meinl E. Persistence of functional memory B cells recognizing SARS-CoV-2 variants despite loss of specific IgG. iScience. 2022 Jan 21;25(1):103659. doi: 10.1016/j.isci.2021.103659.
Schlüter M, Oswald E, Winklmeier S, Meinl I, Havla J, Eichhorn P, Meinl E*, Kümpfel T*.Effects of Natalizumab Therapy on Intrathecal Immunoglobulin G Production Indicate Targeting of Plasmablasts. Neurol Neuroimmunol Neuroinflamm. 2021 Jul 1;8(5):e1030. (* co-senior author)
Nishri Y, Fainstein N, Goldfarb S, Hampton D, Macrini C, Meinl E, Chandran S, Ben-Hur T. Modeling compartmentalized chronic immune-mediated demyelinating CNS disease in the Biozzi ABH mouse. J. Neuroimmunol. 2021, 356:577582.
Macrini C, Gerhards R, Winklmeier S, Bergmann L, Mader S, Spadaro M, Vural A, Smolle M, Hohlfeld R, Kümpfel T, Lichtenthaler S, Franquelim H, Jenne D, Meinl E. Features of MOG required for recognition by patients with MOG-antibody-associated disorders. Brain, 2021, 144(8):2375-2389..
Beltrán E, Paunovic M, Gebert D, Cesur E, Jeitler M, Höftberger R, Malotka J, Mader S, Kawakami N, Meinl E, Bradl M, Dornmair K, Lassmann H. Archeological neuroimmunology: resurrection of a pathogenic immune response from a historical case sheds light on human autoimmune encephalomyelitis and multiple sclerosis. Acta Neuropathol. 2021 Jan;141(1):67-83 Oct 29.
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.
Robinson T, Abdelhak A, Bose T, Meinl E, Otto M, Zettl UK, Dersch R, Tumani H, Rauer S, Huss A. Cerebrospinal Fluid Biomarkers in Relation to MRZ Reaction Status in Primary Progressive Multiple Sclerosis. Cells. 2020 Nov 25;9(12):E2543.
Eslami M, Meinl E, Eibel H, Willen L, Donzé O, Distl O, Schneider H, Speiser DE, Tsiantoulas D, Yalkinoglu Ö, Samy E, Schneider P. BAFF 60-mer, and Differential BAFF 60-mer Dissociating Activities in Human Serum, Cord Blood and Cerebrospinal Fluid. Front Cell Dev Biol. 2020 Nov 6;8:577662.
Liu J, Mori M, Zimmermann H, Brandt A, Havla J, Tanaka S, Sugimoto K, Oji S, Uzawa A, Asseyer S, Cooper G, Jarius S, Bellmann-Strobl J, Ruprecht K, Siebert N, Masuda H, Uchida T, Ohtani R, Nomura K, Meinl E, Kuempfel T, Paul F, Kuwabara S. Anti-MOG antibody-associated disorders: differences in clinical profiles and prognosis in Japan and Germany. J Neurol Neurosurg Psychiatry. 2020 Nov 20:jnnp-2020-324422.
Inan B, Gocmen R, Vural A, Colpak AI, Meinl E, Karabudak R, Tuncer A. Myelin oligodendrocyte glycoprotein antibody associated central nervous system demyelinating disease: a tertiary center experience from Turkey. Mult Scler Relat Disord. 2020 Jul 4;44:102376.
Faissner S, Graz F, Reinehr S, Petrikowski L, Haupeltshofer S, Ceylan U, Stute G, Winklmeier S, Pache F, Paul F, Ruprecht K, Meinl E, Dick HB, Gold R, Kleiter I, Joachim SC. Binding patterns and functional properties of human antibodies to AQP4 and MOG on murine optic nerve and retina. J Neuroimmunol. 2020 Feb 20;342:577194.
Huber JE, Chang Y, Meinl I, Kümpfel T, Meinl E, Baumjohann D. Fingolimod Profoundly Reduces Frequencies and Alters Subset Composition of Circulating T Follicular Helper Cells in Multiple Sclerosis Patients. J Immunol. 2020 Mar 1;204(5):1101-1110.
Mulazzani M, Huber M, Borchard S, Langer S, Angele B, Schuh E, Meinl E, Dreyling M, Birnbaum T, Straube A, Koedel U, von Baumgarten L. APRIL and BAFF: novel biomarkers for central nervous system lymphoma. J Hematol Oncol. 2019 Oct 15;12(1):102.
Winklmeier S, Schlüter M, Spadaro M, Thaler FS, Vural A, Gerhards R, Macrini C, Mader S, Kurne A, Inan B, Karabudak R, Özbay FG, Esendagli G, Hohlfeld R, Kümpfel T, Meinl E. Identification of circulating MOG-specific B cells in patients with MOG antibodies. Neurol Neuroimmunol Neuroinflamm. 2019 Oct 14;6(6):625. Erratum in: Neurol Neuroimmunol Neuroinflamm. 2019 Nov 15;7(1).
Stengel H, Vural A, Brunder AM, Heinius A, Appeltshauser L, Fiebig B, Giese F, Dresel C, Papagianni A, Birklein F, Weis J, Huchtemann T, Schmidt C, Körtvelyessy P, Villmann C, Meinl E, Sommer C, Leypoldt F, Doppler K. Anti-pan-neurofascin IgG3 as a marker of fulminant autoimmune neuropathy. Neurol Neuroimmunol Neuroinflamm. 2019 Aug 16;6(5):e603.
Konjevic Sabolek M, Held K, Beltrán E, Niedl AG, Meinl E, Hohlfeld R, Lassmann H, Dornmair K. Communication of CD8+ T cells with mononuclear phagocytes in multiple sclerosis. Ann Clin Transl Neurol. 2019 Jul;6(7):1151-1164.
Oertel FC, Outteryck O, Knier B, Zimmermann H, Borisow N, Bellmann-Strobl J, Blaschek A, Jarius S, Reindl M, Ruprecht K, Meinl E, Hohlfeld R, Paul F, Brandt AU, Kümpfel T, Havla J. Optical coherence tomography in myelin-oligodendrocyte-glycoprotein antibody-seropositive patients: a longitudinal study. J Neuroinflammation. 2019 Jul 25;16(1):154.
Marti Fernandez I, Macrini C, Krumbholz M, Hensbergen PJ, Hipgrave Ederveen AL, Winklmeier S, Vural A, Kurne A, Jenne D, Kamp F, Gerdes LA, Hohlfeld R, Wuhrer M, Kümpfel T, Meinl E. The Glycosylation Site of Myelin Oligodendrocyte Glycoprotein Affects Autoantibody Recognition in a Large Proportion of Patients. Front Immunol. 2019 Jun 11;10:1189.
Bronge M, Ruhrmann S, Carvalho-Queiroz C, Nilsson OB, Kaiser A, Holmgren E, Macrini C, Winklmeier S, Meinl E, Brundin L, Khademi M, Olsson T, Gafvelin G, Grönlund H. Myelin oligodendrocyte glycoprotein revisited-sensitive detection of MOG-specific T-cells in multiple sclerosis. J Autoimmun. 2019 Aug;102:38-49.
Thaler FS, Thaller AL, Biljecki M, Schuh E, Winklmeier S, Mahler CF, Gerhards R, Völk S, Schnorfeil F, Subklewe M, Hohlfeld R, Kümpfel T, Meinl E. Abundant glutamic acid decarboxylase (GAD)-reactive B cells in gad-antibody-associated neurological disorders. Ann Neurol. 2019 Mar;85(3):448-454.
Harnisch K, Teuber-Hanselmann S, Macha N, Mairinger F, Fritsche L, Soub D, Meinl E, Junker A. Myelination in Multiple Sclerosis Lesions Is Associated with Regulation of Bone Morphogenetic Protein 4 and Its Antagonist Noggin. Int J Mol Sci. 2019 Jan 3;20(1):154.
Spadaro M, Winklmeier S, Beltrán E, Macrini C, Höftberger R, Schuh E, Thaler FS, Gerdes LA, Laurent S, Gerhards R, Brändle S, Dornmair K, Breithaupt C, Krumbholz M, Moser M, Krishnamoorthy G, Kamp F, Jenne D, Hohlfeld R, Kümpfel T, Lassmann H, Kawakami N, Meinl E. Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein. Ann Neurol. 2018 Aug;84(2):315-328.
Doppler K, Stengel H, Appeltshauser L, Grosskreutz J, Man Ng JK, Meinl E, Sommer C. Neurofascin-155 IgM autoantibodies in patients with inflammatory neuropathies. J Neurol Neurosurg Psychiatry. 2018 Nov;89(11):1145-1151.
Diederich JM, Staudt M, Meisel C, Hahn K, Meinl E, Meisel A, Klehmet J. Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes. Front Neurol. 2018 Mar 19;9:171.
Klehmet J, Staudt M, Diederich JM, Siebert E, Meinl E, Harms L, Meisel A. Neurofascin (NF)155- and NF186-Specific T Cell Response in a Patient Developing a Central Pontocerebellar Demyelination after 10 Years of CIDP. Front Neurol. 2017 Dec 22;8:724.
Thaler FS, Laurent SA, Huber M, Mulazzani M, Dreyling M, Ködel U, Kümpfel T, Straube A, Meinl E, von Baumgarten L. Soluble TACI and soluble BCMA as biomarkers in primary central nervous system lymphoma. Neuro Oncol. 2017 Nov 29;19(12):1618-1627.
Schuh E, Musumeci A, Thaler FS, Laurent S, Ellwart JW, Hohlfeld R, Krug A, Meinl E. Human Plasmacytoid Dendritic Cells Display and Shed B Cell Maturation Antigen upon TLR Engagement. J Immunol. 2017 Apr 15;198(8):3081-3088.
Romanelli E, Merkler D, Mezydlo A, Weil MT, Weber MS, Nikić I, Potz S, Meinl E, Matznick FE, Kreutzfeldt M, Ghanem A, Conzelmann KK, Metz I, Brück W, Routh M, Simons M, Bishop D, Misgeld T, Kerschensteiner M. Myelinosome formation represents an early stage of oligodendrocyte damage in multiple sclerosis and its animal model. Nat Commun. 2016 Nov 16;7:13275.
Havla J, Kümpfel T, Schinner R, Spadaro M, Schuh E, Meinl E, Hohlfeld R, Outteryck O. Myelin-oligodendrocyte-glycoprotein (MOG) autoantibodies as potential markers of severe optic neuritis and subclinical retinal axonal degeneration. J Neurol. 2017 Jan;264(1):139-151.
Spadaro M, Gerdes LA, Krumbholz M, Ertl-Wagner B, Thaler FS, Schuh E, Metz I, Blaschek A, Dick A, Brück W, Hohlfeld R, Meinl E*, Kümpfel T. Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2016 Jun 30;3(5):e257. (* co-senior author)
Schuh E, Berer K, Mulazzani M, Feil K, Meinl I, Lahm H, Krane M, Lange R, Pfannes K, Subklewe M, Gürkov R, Bradl M, Hohlfeld R, Kümpfel T, Meinl E*, Krumbholz M. Features of Human CD3+CD20+ T Cells. J Immunol. 2016 Aug 15;197(4):1111-7. (* co-senior author)
Flytzani S, Guerreiro-Cacais AO, N'diaye M, Lindner M, Linington C, Meinl E, Stridh P, Jagodic M, Olsson T. MOG-induced experimental autoimmune encephalomyelitis in the rat species triggers anti-neurofascin antibody response that is genetically regulated. J Neuroinflammation. 2015 Oct 29;12:194.
Ligocki AJ, Rivas JR, Rounds WH, Guzman AA, Li M, Spadaro M, Lahey L, Chen D, Henson PM, Graves D, Greenberg BM, Frohman EM, Ward ES, Robinson W, Meinl E, White CL 3rd, Stowe AM, Monson NL. A Distinct Class of Antibodies May Be an Indicator of Gray Matter Autoimmunity in Early and Established Relapsing Remitting Multiple Sclerosis Patients. ASN Neuro. 2015 Oct 21;7(5):1759091415609613.
Hoffmann FS, Hofereiter J, Rübsamen H, Melms J, Schwarz S, Faber H, Weber P, Pütz B, Loleit V, Weber F, Hohlfeld R, Meinl E*, Krumbholz M. Fingolimod induces neuroprotective factors in human astrocytes. J Neuroinflammation. 2015 Sep 30;12:184. (* co-senior author)
Vural A, Göçmen R, Kurne AT, Oğuz KK, Temuçin ÇM, Tan E, Karabudak R, Meinl E, Erdem Özdamar S. Fulminant Central Plus Peripheral Nervous System Demyelination without Antibodies to Neurofascin. Can J Neurol Sci. 2016 Jan;43(1):149-56.
Doppler K, Appeltshauser L, Krämer HH, Ng JK, Meinl E, Villmann C, Brophy P, Dib-Hajj SD, Waxman SG, Weishaupt A, Sommer C. Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto-Antibodies in Multifocal Motor Neuropathy. PLoS One. 2015 Jul 28;10(7):e0134274.
Wuhrer M, Selman MH, McDonnell LA, Kümpfel T, Derfuss T, Khademi M, Olsson T, Hohlfeld R, Meinl E, Krumbholz M. Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. J Neuroinflammation. 2015 Dec 18;12:235.
Laurent SA, Hoffmann FS, Kuhn PH, Cheng Q, Chu Y, Schmidt-Supprian M, Hauck SM, Schuh E, Krumbholz M, Rübsamen H, Wanngren J, Khademi M, Olsson T, Alexander T, Hiepe F, Pfister HW, Weber F, Jenne D, Wekerle H, Hohlfeld R, Lichtenthaler SF, Meinl E. γ-Secretase directly sheds the survival receptor BCMA from plasma cells. Nat Commun. 2015 Jun 11;6:7333.
Lindner M, Thümmler K, Arthur A, Brunner S, Elliott C, McElroy D, Mohan H, Williams A, Edgar JM, Schuh C, Stadelmann C, Barnett SC, Lassmann H, Mücklisch S, Mudaliar M, Schaeren-Wiemers N, Meinl E*, Linington C. Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9. Brain. 2015 Jul;138(Pt 7):1875-93. (* co-senior author)
Spadaro M, Gerdes LA, Mayer MC, Ertl-Wagner B, Laurent S, Krumbholz M, Breithaupt C, Högen T, Straube A, Giese A, Hohlfeld R, Lassmann H, Meinl E*, Kümpfel T. Histopathology and clinical course of MOG-antibody-associated encephalomyelitis. Ann Clin Transl Neurol. 2015 Mar;2(3):295-301. (* co-senior author)
Mohan H, Friese A, Albrecht S, Krumbholz M, Elliott CL, Arthur A, Menon R, Farina C, Junker A, Stadelmann C, Barnett SC, Huitinga I, Wekerle H, Hohlfeld R, Lassmann H, Kuhlmann T, Linington C, Meinl E. Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination. Acta Neuropathol Commun. 2014 Dec 11;2:168.
Hoffmann FS, Kuhn PH, Laurent SA, Hauck SM, Berer K, Wendlinger SA, Krumbholz M, Khademi M, Olsson T, Dreyling M, Pfister HW, Alexander T, Hiepe F, Kümpfel T, Crawford HC, Wekerle H, Hohlfeld R, Lichtenthaler SF, Meinl E. The immunoregulator soluble TACI is released by ADAM10 and reflects B cell activation in autoimmunity. J Immunol. 2015 Jan 15;194(2):542-52.
Shen P, Roch T, Lampropoulou V, O'Connor RA, Stervbo U, Hilgenberg E, Ries S, Dang VD, Jaimes Y, Daridon C, Li R, Jouneau L, Boudinot P, Wilantri S, Sakwa I, Miyazaki Y, Leech MD, McPherson RC, Wirtz S, Neurath M, Hoehlig K, Meinl E, Grützkau A, Grün JR, Horn K, Kühl AA, Dörner T, Bar-Or A, Kaufmann SHE, Anderton SM, Fillatreau S. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature. 2014 Mar 20;507(7492):366-370.
Mayer MC, Breithaupt C, Reindl M, Schanda K, Rostásy K, Berger T, Dale RC, Brilot F, Olsson T, Jenne D, Pröbstel AK, Dornmair K, Wekerle H, Hohlfeld R, Banwell B, Bar-Or A, Meinl E. Distinction and temporal stability of conformational epitopes on myelin oligodendrocyte glycoprotein recognized by patients with different inflammatory central nervous system diseases. J Immunol. 2013 Oct 1;191(7):3594-604.
Lindner M, Ng JK, Hochmeister S, Meinl E, Linington C. Neurofascin 186 specific autoantibodies induce axonal injury and exacerbate disease severity in experimental autoimmune encephalomyelitis. Exp Neurol. 2013 Sep;247:259-66.
Ng JK, Malotka J, Kawakami N, Derfuss T, Khademi M, Olsson T, Linington C, Odaka M, Tackenberg B, Prüss H, Schwab JM, Harms L, Harms H, Sommer C, Rasband MN, Eshed-Eisenbach Y, Peles E, Hohlfeld R, Yuki N, Dornmair K, Meinl E. Neurofascin as a target for autoantibodies in peripheral neuropathies. Neurology. 2012 Dec 4;79(23):2241-8.
Elliott C, Lindner M, Arthur A, Brennan K, Jarius S, Hussey J, Chan A, Stroet A, Olsson T, Willison H, Barnett SC, Meinl E, Linington C. Functional identification of pathogenic autoantibody responses in patients with multiple sclerosis. Brain. 2012 Jun;135(Pt 6):1819-33.
Colombo E, Cordiglieri C, Melli G, Newcombe J, Krumbholz M, Parada LF, Medico E, Hohlfeld R, Meinl E, Farina C. Stimulation of the neurotrophin receptor TrkB on astrocytes drives nitric oxide production and neurodegeneration. J Exp Med. 2012 Mar 12;209(3):521-35.
Eisele S, Krumbholz M, Fischer MT, Mohan H, Junker A, Arzberger T, Hohlfeld R, Bradl M, Lassmann H, Meinl E. Prospects of transcript profiling for mRNAs and MicroRNAs using formalin-fixed and paraffin-embedded dissected autoptic multiple sclerosis lesions. Brain Pathol. 2012 Sep;22(5):607-18.
Pröbstel AK, Dornmair K, Bittner R, Sperl P, Jenne D, Magalhaes S, Villalobos A, Breithaupt C, Weissert R, Jacob U, Krumbholz M, Kuempfel T, Blaschek A, Stark W, Gärtner J, Pohl D, Rostasy K, Weber F, Forne I, Khademi M, Olsson T, Brilot F, Tantsis E, Dale RC, Wekerle H, Hohlfeld R, Banwell B, Bar-Or A, Meinl E*, Derfuss T. Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology. 2011 Aug 9;77(6):580-8. (* co-senior author)
Held K, Junker A, Dornmair K, Meinl E, Sinicina I, Brandt T, Theil D, Derfuss T. Expression of herpes simplex virus 1-encoded microRNAs in human trigeminal ganglia and their relation to local T-cell infiltrates. J Virol. 2011 Oct;85(19):9680-5.
Pellkofer HL, Krumbholz M, Berthele A, Hemmer B, Gerdes LA, Havla J, Bittner R, Canis M, Meinl E, Hohlfeld R, Kuempfel T. Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab. Neurology. 2011 Apr 12;76(15):1310-5.
Mohan H, Krumbholz M, Sharma R, Eisele S, Junker A, Sixt M, Newcombe J, Wekerle H, Hohlfeld R, Lassmann H, Meinl E. Extracellular matrix in multiple sclerosis lesions: Fibrillar collagens, biglycan and decorin are upregulated and associated with infiltrating immune cells. Brain Pathol. 2010 Sep;20(5):966-75.
Junker A, Krumbholz M, Eisele S, Mohan H, Augstein F, Bittner R, Lassmann H, Wekerle H, Hohlfeld R, Meinl E. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain. 2009 Dec;132(Pt 12):3342-52.
Derfuss T, Parikh K, Velhin S, Braun M, Mathey E, Krumbholz M, Kümpfel T, Moldenhauer A, Rader C, Sonderegger P, Pöllmann W, Tiefenthaller C, Bauer J, Lassmann H, Wekerle H, Karagogeos D, Hohlfeld R, Linington C, Meinl E. Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8302-7.
Krumbholz M, Meinl I, Kümpfel T, Hohlfeld R, Meinl E. Natalizumab disproportionately increases circulating pre-B and B cells in multiple sclerosis. Neurology. 2008 Oct 21;71(17):1350-4.
Berzi A, Ayata CK, Cavalcante P, Falcone C, Candiago E, Motta T, Bernasconi P, Hohlfeld R, Mantegazza R, Meinl E, Farina C. BDNF and its receptors in human myasthenic thymus: implications for cell fate in thymic pathology. J Neuroimmunol. 2008 Jul 15;197(2):128-39.
Krumbholz M, Faber H, Steinmeyer F, Hoffmann LA, Kümpfel T, Pellkofer H, Derfuss T, Ionescu C, Starck M, Hafner C, Hohlfeld R, Meinl E. Interferon-beta increases BAFF levels in multiple sclerosis: implications for B cell autoimmunity. Brain. 2008 Jun;131(Pt 6):1455-63.
Kuhl A, Melberg A, Meinl E, Nürnberg G, Nürnberg P, Kehrer-Sawatzki H, Jenne DE. Myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7: corroboration and narrowing of the critical region on 10q22.3. Eur J Hum Genet. 2008 Mar;16(3):367-73.
Junker A, Ivanidze J, Malotka J, Eiglmeier I, Lassmann H, Wekerle H, Meinl E, Hohlfeld R, Dornmair K. Multiple sclerosis: T-cell receptor expression in distinct brain regions. Brain. 2007 Nov;130(Pt 11):2789-99.
Mathey EK, Derfuss T, Storch MK, Williams KR, Hales K, Woolley DR, Al-Hayani A, Davies SN, Rasband MN, Olsson T, Moldenhauer A, Velhin S, Hohlfeld R, Meinl E*, Linington C. Neurofascin as a novel target for autoantibody-mediated axonal injury. J Exp Med. 2007 Oct 1;204(10):2363-72. (* co-senior author)
Krumbholz M, Theil D, Steinmeyer F, Cepok S, Hemmer B, Hofbauer M, Farina C, Derfuss T, Junker A, Arzberger T, Sinicina I, Hartle C, Newcombe J, Hohlfeld R, Meinl E. CCL19 is constitutively expressed in the CNS, up-regulated in neuroinflammation, active and also inactive multiple sclerosis lesions. J Neuroimmunol. 2007 Oct;190(1-2):72-9.
Derfuss T, Segerer S, Herberger S, Sinicina I, Hüfner K, Ebelt K, Knaus HG, Steiner I, Meinl E, Dornmair K, Arbusow V, Strupp M, Brandt T, Theil D. Presence of HSV-1 immediate early genes and clonally expanded T-cells with a memory effector phenotype in human trigeminal ganglia. Brain Pathol. 2007 Oct;17(4):389-98.
Hoffmann LA, Krumbholz M, Faber H, Kuempfel T, Starck M, Pöllmann W, Meinl E, Hohlfeld R. Multiple sclerosis: relating MxA transcription to anti-interferon-beta-neutralizing antibodies. Neurology. 2007 Mar 20;68(12):958-9.
Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisäkk P, Ransohoff RM, Hofbauer M, Farina C, Derfuss T, Hartle C, Newcombe J, Hohlfeld R, Meinl E. Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain. 2006 Jan;129(Pt 1):200-11.
Krumbholz M, Specks U, Wick M, Kalled SL, Jenne D, Meinl E. BAFF is elevated in serum of patients with Wegener's granulomatosis. J Autoimmun. 2005 Dec;25(4):298-302.
Vargas-Leal V, Bruno R, Derfuss T, Krumbholz M, Hohlfeld R, Meinl E. Expression and function of glial cell line-derived neurotrophic factor family ligands and their receptors on human immune cells. J Immunol. 2005 Aug 15;175(4):2301-8.
Farina C, Krumbholz M, Giese T, Hartmann G, Aloisi F, Meinl E. Preferential expression and function of Toll-like receptor 3 in human astrocytes. J Neuroimmunol. 2005 Feb;159(1-2):12-
Krumbholz M, Theil D, Derfuss T, Rosenwald A, Schrader F, Monoranu CM, Kalled SL, Hess DM, Serafini B, Aloisi F, Wekerle H, Hohlfeld R, Meinl E. BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J Exp Med. 2005 Jan 17;201(2):195-200.
Derfuss T, Hohlfeld R, Meinl E. Intrathecal antibody (IgG) production against human herpesvirus type 6 occurs in about 20% of multiple sclerosis patients and might be linked to a polyspecific B-cell response. J Neurol. 2005 Aug;252(8):968-71.
Theil D, Farina C, Meinl E. Differential expression of CD150 (SLAM) on monocytes and macrophages in chronic inflammatory contexts: abundant in Crohn's disease, but not in multiple sclerosis. J Clin Pathol. 2005 Jan;58(1):110-1.
Farina C, Theil D, Semlinger B, Hohlfeld R, Meinl E. Distinct responses of monocytes to Toll-like receptor ligands and inflammatory cytokines. Int Immunol. 2004 Jun;16(6):799-809.
Weber MS, Starck M, Wagenpfeil S, Meinl E, Hohlfeld R, Farina C. Multiple sclerosis: glatiramer acetate inhibits monocyte reactivity in vitro and in vivo. Brain. 2004 Jun;127(Pt 6):1370-8.
Theil D, Derfuss T, Paripovic I, Herberger S, Meinl E, Schueler O, Strupp M, Arbusow V, Brandt T. Latent herpesvirus infection in human trigeminal ganglia causes chronic immune response. Am J Pathol. 2003 Dec;163(6):2179-84.
Farina C, Vargas V, Heydari N, Kümpfel T, Meinl E, Hohlfeld R. Treatment with glatiramer acetate induces specific IgG4 antibodies in multiple sclerosis patients. J Neuroimmunol. 2002 Feb;123(1-2):188-92.
Derfuss T, Gürkov R, Then Bergh F, Goebels N, Hartmann M, Barz C, Wilske B, Autenrieth I, Wick M, Hohlfeld R, Meinl E. Intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis is part of a polyspecific immune response. Brain. 2001 Jul;124(Pt 7):1325-35.
Farina C, Then Bergh F, Albrecht H, Meinl E, Yassouridis A, Neuhaus O, Hohlfeld R. Treatment of multiple sclerosis with Copaxone (COP): Elispot assay detects COP-induced interleukin-4 and interferon-gamma response in blood cells. Brain. 2001 Apr;124(Pt 4):705-19.
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Boldrini, V. O., Mader, S., Kümpfel, T., & Meinl, E. (2023). Ublituximab: A new FDA-approved anti-CD20 mAb for relapsing forms of multiple sclerosis. Mult scler relat disord, 75, 104733.
Thaler FS, Meinl E. Cytotoxic T cells and plasma cells dominate early in temporal lobe epilepsy with GAD antibodies. Brain. 2023 Apr 19;146(4):1231-1233. doi: 10.1093/brain/awad066. Erratum in: Brain. 2023 Apr 17;: PMID: 36864690
Meinl E. Multiple Sklerose und Epstein-Barr Virus: gesicherte Erkenntnisse und offene Fragen. Neurodiem 2022
Mader S, Kümpfel T, Meinl E. Pathomechanisms in demyelination and astrocytopathy: autoantibodies to AQP4, MOG, GFAP, GRP78 and beyond. Curr Opin Neurol. 2022 Jun 1;35(3):427-435.
Meinl E, Hohlfeld R. CD20+ T Cells as Pathogenic Players and Therapeutic Targets in MS. Ann Neurol. 2021 Nov;90(5):722-724.
Meinl E, Krumbholz M. Endogenous soluble receptors sBCMA and sTACI: biomarker, immunoregulator and hurdle for therapy in multiple myeloma. Curr Opin Immunol. 2021 Aug;71:117-123.
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.
Lichtenthaler SF, Meinl E. To cut or not to cut: New rules for proteolytic shedding of membrane proteins. J Biol Chem. 2020 Aug 28;295(35):12353-12354.
Mader S, Kümpfel T, Meinl E. Novel insights into pathophysiology and therapeutic possibilities reveal further differences between AQP4-IgG- and MOG-IgG-associated diseases. Curr Opin Neurol. 2020 Jun;33(3):362-371.
Teuber-Hanselmann S, Meinl E, Junker A. MicroRNAs in gray and white matter multiple sclerosis lesions: impact on pathophysiology. J Pathol. 2020 Apr;250(5):496-509.
Meinl E, Thaler FS, Lichtenthaler SF. Shedding of BAFF/APRIL Receptors Controls B Cells. Trends Immunol. 2018 Sep;39(9):673-676.
Vural A, Doppler K, Meinl E. Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance. Front Immunol. 2018 May 14;9:1029.
Hohlfeld R, Meinl E. Ocrelizumab in multiple sclerosis: markers and mechanisms. Lancet Neurol. 2017 Apr;16(4):259-261.
Hohlfeld R, Dornmair K, Meinl E, Wekerle H. The search for the target antigens of multiple sclerosis, part 1: autoreactive CD4+ T lymphocytes as pathogenic effectors and therapeutic targets. Lancet Neurol. 2016 Feb;15(2):198-209.
Hohlfeld R, Dornmair K, Meinl E, Wekerle H. The search for the target antigens of multiple sclerosis, part 2: CD8+ T cells, B cells, and antibodies in the focus of reverse-translational research. Lancet Neurol. 2016 Mar;15(3):317-31.
Spadaro M, Meinl E. Detection of Autoantibodies Against Myelin Oligodendrocyte Glycoprotein in Multiple Sclerosis and Related Diseases. Methods Mol Biol. 2016;1304:99-104.
Krumbholz M, Meinl E. B cells in MS and NMO: pathogenesis and therapy. Semin Immunopathol. 2014 May;36(3):339-50.
Hoffmann F, Meinl E. B cells in multiple sclerosis: good or bad guys?: An article for 28 May 2014 - World MS Day 2014. Eur J Immunol. 2014 May;44(5):1247-50.
Wekerle H, Meinl E. Multiple sclerosis: An old drug plays a new trick. Nature. 2013 Oct 17;502(7471):314-5.
Stangel M, Fredrikson S, Meinl E, Petzold A, Stüve O, Tumani H. The utility of cerebrospinal fluid analysis in patients with multiple sclerosis. Nat Rev Neurol. 2013 May;9(5):267-76.
Meinl E, Meister G. MicroRNAs in the CSF: macro-advance in MS? Neurology. 2012 Nov 27;79(22):2162-3.
Krumbholz M, Derfuss T, Hohlfeld R, Meinl E. B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol. 2012 Nov 5;8(11):613-23.
Mayer MC, Hohlfeld R, Meinl E. Viability of autoantibody-targets: how to tackle pathogenetic heterogeneity as an obstacle for treatment of multiple sclerosis. J Neurol Sci. 2012 Aug 15;319(1-2):2-7.
Mayer MC, Meinl E. Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more. Ther Adv Neurol Disord. 2012 May;5(3):147-59.
Derfuss T, Meinl E. Identifying autoantigens in demyelinating diseases: valuable clues to diagnosis and treatment? Curr Opin Neurol. 2012 Jun;25(3):231-8.
Meinl E. Untapped targets in multiple sclerosis. J Neurol Sci. 2011 Dec;311 Suppl 1:S12-5.
Meinl E, Derfuss T, Krumbholz M, Pröbstel AK, Hohlfeld R. Humoral autoimmunity in multiple sclerosis. J Neurol Sci. 2011 Jul 15;306(1-2):180-2.
Derfuss T, Linington C, Hohlfeld R, Meinl E. Axo-glial antigens as targets in multiple sclerosis: implications for axonal and grey matter injury. J Mol Med (Berl). 2010 Aug;88(8):753-61.
Dornmair K, Meinl E, Hohlfeld R. Novel approaches for identifying target antigens of autoreactive human B and T cells. Semin Immunopathol. 2009 Nov;31(4):467-77.
Kerschensteiner M, Meinl E, Hohlfeld R. Neuro-immune crosstalk in CNS diseases. Neuroscience. 2009 Feb 6;158(3):1122-32.
Meinl E, Krumbholz M, Derfuss T, Junker A, Hohlfeld R. Compartmentalization of inflammation in the CNS: a major mechanism driving progressive multiple sclerosis. J Neurol Sci. 2008 Nov 15;274(1-2):42-4.
Hohlfeld R, Meinl E, Dornmair K. B- and T-cell responses in multiple sclerosis: novel approaches offer new insights. J Neurol Sci. 2008 Nov 15;274(1-2):5-8.
Farina C, Aloisi F, Meinl E. Astrocytes are active players in cerebral innate immunity. Trends Immunol. 2007 Mar;28(3):138-45.
Hohlfeld R, Kerschensteiner M, Meinl E. Dual role of inflammation in CNS disease. Neurology. 2007 May 29;68(22 Suppl 3):S58-63; discussion S91-6.
Meinl E, Krumbholz M, Hohlfeld R. B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation. Ann Neurol. 2006 Jun;59(6):880-92.
Farina C, Weber MS, Meinl E, Wekerle H, Hohlfeld R. Glatiramer acetate in multiple sclerosis: update on potential mechanisms of action. Lancet Neurol. 2005 Sep;4(9):567-75.
Meinl E, Voltz R. Biomarker in der Therapie der Multiplen Sklerose. Lässt sich der Erfolg bald vorhersagen? [Multiple sclerosis. Biomarkers for deciding treatment]. MMW Fortschr Med. 2004 May 24;146 Spec No 2:57-8. German.
Derfuss T, Meinl E. Herpesviral proteins regulating apoptosis. Curr Top Microbiol Immunol. 2002;269:257-72.
Meinl E, Hohlfeld R. Immunopathogenesis of multiple sclerosis: MBP and beyond. Clin Exp Immunol. 2002 Jun;128(3):395-7.
Derfuss T, Hohlfeld R, Meinl E. Multiple Sklerose. Chlamydien-Hypothese in der Diskussion [Multiple sclerosis. Chlamydia hypothesis in debate]. Nervenarzt. 2001 Oct;72(10):820-3. German.
Meinl E, Hohlfeld R. T cell transformation with Herpesvirus saimiri: a tool for neuroimmunological research. J Neuroimmunol. 2000 Feb 1;103(1):1-7.
Meinl E. Concepts of viral pathogenesis of multiple sclerosis. Curr Opin Neurol. 1999 Jun;12(3):303-7.
Meinl E, Fickenscher H, Thome M, Tschopp J, Fleckenstein B. Anti-apoptotic strategies of lymphotropic viruses. Immunol Today. 1998 Oct;19(10):474-9.
Tschopp J, Thome M, Hofmann K, Meinl E. The fight of viruses against apoptosis. Curr Opin Genet Dev. 1998 Feb;8(1):82-7.
Meinl E, Fickenscher H, Fleckenstein B. Chemokine receptors and chemokine-inducing molecules of lymphotropic herpesviruses. Immunol Today. 1996 Apr;17(4):199.
Hohlfeld R, Meinl E, Weber F, Zipp F, Schmidt S, Sotgiu S, Goebels N, Voltz R, Spuler S, Iglesias A, et al. The role of autoimmune T lymphocytes in the pathogenesis of multiple sclerosis. Neurology. 1995 Jun;45(6 Suppl 6):S33-8.
Meinl E, Hohlfeld R, Wekerle H, Fleckenstein B. Immortalization of human T cells by Herpesvirus saimiri. Immunol Today. 1995 Feb;16(2):55-8.
Edgar Meinl, Principal Investigator
Read more about the PI on the next tab.
Simone Mader, leader of the associated Junior group. Junior group Mader
I completed my PhD at the Medical University of Innsbruck in the Department of Neurology. For my PhD studies, I have been working on autoantibodies in Multiple Sclerosis and Neuromyelitis optica spectrum disorders (NMOSD). My work focused on AQP4 antibodies and their relevance for disease pathogenesis and we could report for the first time that MOG antibodies are present in a subgroup of AQP4-IgG seronegative NMOSD. As a Post-Doc, I joined the lab of Dr. Betty Diamond at the Feinstein Institute in New York, where I have been studying anti-brain antibodies in disease and pregnancy. We could show that maternal autoantibodies induce autism-like phenotype in mice and identified a novel antigen. In 2018, I moved from the USA to Munich and I joined the Institute of Clinical Neuroimmunology, AG Meinl. I obtained funding such as from the Else Kröner-Fresenius-Stiftung (EKFS) or the Schering Stiftung and Fritz Thyssen Foundation, to continue working on novel antigen discovery in different neurological diseases. I am currently also writing my habilitation and supervising students. When I am not working in the lab, I enjoy hiking in the nature and spending time with my family and friends.
Stephan Winklmeier, Posdoctoral fellow
After pursuing my Bachelor's study in Biology at LMU, I conducted my Master's study in Biochemistry at LMU/Harvard Medical School and worked in Biophysics at TUM. In 2016, I joined the Meinl lab for my PhD. From the very beginning, I was fascinated by the research with human material in such an interdisciplinary environment closely connected to the clinic. In addition, I enjoy the teamwork in such a nice and friendly working atmosphere here. My main focus during my PhD was directed to the detection and characterization of auto-antibodies and auto-reactive B cells, especially, against the myelin oligodendrocyte glycoprotein (MOG) and its pathological role in patients. In 2021, I obtained the PhD degree, and now I am continuing my research in the Meinl lab. Besides tackling questions in antibody-mediated CNS autoimmunity, we additionally aim to understand the protective immunity against SARS-CoV-2 in patients treated with immunosuppressive therapy. When I am not in the lab, I love to go hiking, to capture motives with my camera and to hang out with friends, or you may find me somewhere in the sea snorkeling/diving.
Charlotte Schadt, Medical student
I started studying medicine at the LMU in 2015. As part of my studies, I did a clinical internship at the neurology department. After seeing many patients with neuroimmunological diseases like multiple sclerosis, I wanted to get a closer look at the topic. I was always interested in an experimental thesis, so I was happy to join the Meinl lab for my MD thesis within the FöFoLe-project of the LMU. Besides learning new techniques like flow-cytometry and ELISA, I really enjoy working together with an international team with great teamwork and mutual support. I am focusing on the role of the BAFF-APRIL-System in multiple sclerosis in my MD thesis. To unwind, I love to go bike riding, do yoga or bake, preferably accompanied by friends or family.
Heike Rübsamen, Laboratory technician
I started my work as a biological technical assistant in 1992 in the LMU clinic directly after my education. Since then, I have been part of three different working groups, of which, my current work resides in Prof. Edgar Meinl`s group since 2011. My technical expertise are in immunoassays, cell culture, protein production and purification, quantitative PCR. In addition, I also manage the infrastructure of the lab as well as organizational issues along with all the small things to keep a lab running.
Selia Baier, PhD Student
After a job training as a pharmaceutical-technical assistant, I was very interested in biology and medicine, and decided to catch up on my high school diploma and start a bachelor's degree in Bioengineering at HM Munich in 2012. During a 6-month internship and my bachelor thesis, I studied the characteristics of proteins translated from therapeutic mRNA. This project raised my interest for immunology. In 2016, I continued my scientific career at TU Munich in the master Molecular Biotechnology, specializing in immunology and neurobiology. I was able to write my master thesis in 2019 supervised by Prof. Edgar Meinl and Dr. Simone Mader at BMC about the effector mechanisms of a recombinant autoantibodies targeting the myeloid oligodendrocyte glycoprotein (MOG) applying techniques like flow cytometry cell-based assay, ELISA, antibody production and molecular cloning. From 2019 to 2022, I was involved in the development of a platform for a novel CAR T cell therapy at Juno Therapeutics (BMS) and intensively worked on cell purification and characterization as well as virus transduction. However, my main interest was still in the area of neuroimmunology and in September 2022, I had the opportunity to return to BMC and started my PhD thesis in the group of Prof. Edgar Meinl. This project continues my master thesis project and investigates the pathomechanisms and immunomodulatory therapy in CNS inflammatory diseases. In my free time, I love to meet with friends, cook, and play board games. I also enjoy hiking and doing yoga regularly.
Dr Vinicius Boldrini, Post-doctoral fellow
After my bachelor's in biological sciences, I completed my master's and PhD in Immunology at the University of Campinas (UNICAMP) in Brazil. In partnership with the Department of Neurology, I could be in close contact with neurologists and study patients with Multiple Sclerosis (MS) and Neuromyelitis Optica (NMOSD). Part of my research was awarded in Brazil (including by the Brazilian Academy of Neurology - BAN) and internationally (Young Investigator Award, in 2021, by the European Charcot Foundation - ECF).
After a brief period in the United Kingdom - to intensify scientific collaborations between UNICAMP and Cardiff University/Wales -, I had the pleasure of being sponsored by the collaborative CAPES (Brazilian funding agency)/Alexander von Humboldt (AvH) Foundation call for a postdoctoral fellowship in Germany. Hosted by Prof. Edgar Meinl and PD Simone Mader at LMU, I aim to contribute to the group's ongoing research regarding the characterization of B cells and autoantibodies during neuroimmunological conditions. In my free time, I enjoy reading philosophy, being with my family and friends, and watching live performances of rock'n'roll, jazz, or blues.
Prof. Dr. med. Edgar Meinl
I am interested in interactions between the immune system and the nervous system since medical school. I was educated in ImmunoIogy during my thesis (supervised by Hartmut Wekerle) at the Clinical Research Unit for Multiple Sclerosis (MS) of the Max-Planck-Society in Würzburg. Subsequently, I joined the lab of Reinhard Hohlfeld at the Max-Planck-Institute of Psychiatry in Martinsried and studied myelin-reactive T cells from MS patients and their interactions with astrocytes. Then I moved to the Institute of Clinical and Molecular Virology in Erlangen, where I analyzed cell death regulation and transformation by lymphotropic herpesviruses. In 1999, I came back to Martinsried to the newly founded Institute of Clinical Neuroimmunology. Research in my lab addresses the immunopathogenesis of MS and related disorders. We focus on the milieu in inflammatory brain lesions, stratification of patients based on autoantibodies and mechanisms of action of immunomodulatory agents.
Training and scientific vita:
1981 – 1987 Medical studies at the Justus-Liebig-University Gießen
1988 – 1989 Postgraduate at the Clinical Research Unit for Multiple Sclerosis of the Max-Planck-Society in Würzburg.
1990 MD thesis (summa cum laude)
1991 – 1994 Postdoctoral fellow and research assistant at the Max-Planck-Institute of Psychiatry, Martinsried
1994 – 1999 Group leader at the Institute of Clinical und Molecular Virology of the University Erlangen-Nürnberg
1996 Habilitation in Virology, University Erlangen-Nürnberg
Since 1999 Group leader at the Institute of Clinical Neuroimmunology, Ludwig-Maximilans-Universität (LMU) Munich
2003 Habilitation in Neuroimmunology, LMU Munich
Since 2003 Professor (apl) at the Institute of Clinical Neuroimmunology, LMU Munich
Collaborative research
1996 – 2000 Member of the SFB 466 “Lymphocyte activation and viral immunodeficiency”
2001 – 2011 Member of the SFB 571 “Autoimmune reactions: From manifestations and mechanisms to therapy”
2001 – 2004 Member of the GRK 688 “Neurotraumatology”
2009 – 2020 Member of the Competence Network “Multiple Sclerosis” supported by the Federal Ministry of Research and Education (BMBF)
2016 – 2019 Centres of Excellence in Neurodegeneration Pathfinder II Awards
Since 2012 Member of the SFB TR-128 “Initiating/effector versus regulatory mechanisms in Multiple Sclerosis – progress towards tackling the disease”
Editorial activities
Since 2009 Clinical and Experimental Neuroimmunology (Editorial Board)
Since 2010 Journal of Pathology (Editorial Board)
Since 2014 PLOS One (Academic Editor)
Since 2015 Journal of Biological Chemistry (Reviewing Editor)
Since 2017 Frontiers in Neurology and - in Immunology (Associate Editor)
Kicker's competition winners - Christmas 2022
Christmas 2022
Chritmas 2022
Oktoberfest 2022
Good bye Laura !!
Lab outing 2022
Lab outing 2022
Michele's defense party 2022
Meinl Lab 2020
July 2020: Ramona‘s PhD
July 2020: Ramona‘s PhD
Lab 2019
Lab retreat
Lab impression
Lab 2016
We gratefully acknowledge support for our work by the following agencies:
Collaborative Research Center 128 – German Research Foundation (DFG)
Klinisches Kompetenznetzwerk für Multiple Sklerose des BMBF
Verein zur Therapieforschung für MS Kranke
Werner Reichenberger Stiftung
Förderprogramm für Forschung und Lehre (FöFoLe) Der Medizinischen Fakultät der LMU
Merck KGaA
Novartis Pharma GmbH
Roche Pharma AG
Glycoera
Alexion
COVIM
