Importance of peripheral immune tolerance mechanisms for the immunopathogenesis of MS

Multiple sclerosis (MS) is caused by a predominantly T cell-mediated autoimmune reaction against myelin antigens initiated by systemic activation of autoreactive T lymphocytes. Our work addresses mechanisms that are important for the maintenance of peripheral immune tolerance, such as naïve T cell homeostasis and the functional capacity of regulatory T cells (Treg). We are investigating in adults as well as in children and adolescents with MS the influence of T cell neogenesis on these parameters, the mechanism of action of Treg and their susceptibility to pharmacological modulation, and the distribution and activation level of Treg in inflammatory lesions of the brain. 

ALTERATION OF B-CELL HOMEOSTASIS IN PATIENTS WITH MS

The role of B lymphocytes in the immunopathogenesis of MS is increasingly becoming the focus of clinical research. Not least the therapeutic successes with B-cell-depleting drugs (rituximab), show that B cells contribute decisively to the disease progression of MS. One focus of our research is the composition and interaction of B-cell subpopulations in blood and cerebrospinal fluid at different stages of the disease as well as the therapeutic influenceability of B-cells under progression-modifying therapy with immunomodulatory substances.

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Bedeutung peripherer Immuntoleranzmechanismen für die Immunpathogenese der MS

Die Multiple Sklerose (MS) wird durch eine überwiegend T-Zell-vermittelte Autoimmunreaktion gegen Myelinantigene hervorgerufen, die durch systemische Aktivierung autoreaktiver T-Lymphozyten initiiert wird. Unsere Arbeiten befassen sich mit Mechanismen, die für die Aufrechterhaltung der peripheren Immuntoleranz bedeutsam sind, wie zum Beispiel die naive T-Zellhomöostase und die Funktionstüchtigkeit regulatorischer T-Zellen (Treg). Wir untersuchen bei Erwachsenen sowie auch bei Kindern und Jugendlichen mit MS den Einfluss der T-Zellneogenese auf diese Parameter, den Wirkmechanismus von Treg und deren Suszeptibilität gegenüber pharmakologischer Modulation sowie die Verteilung und den Aktivierungsgrad von Treg in entzündlichen Läsionen des Gehirns.

Alteration der B-Zell-Homöostase bei Patienten mit MS

Die Rolle der B-Lymphozyten für die Immunpathogenese der MS rückt zunehmend in den Fokus der klinischen Forschung. Nicht zuletzt die Therapieerfolge mit B-Zell-depletierenden Medikamenten (Rituximab), zeigen, dass B-Zellen entscheidend zur Krankheitsprogression der MS beitragen. Ein Schwerpunkt unserer Forschung ist die Zusammensetzung und das Zusammenspiel von B-Zellsubpopulationen in Blut und Liquor in verschiedenen Stadien der Erkrankung sowie die therapeutische Beeinflussbarkeit von B-Zellen unter verlaufsmodifizierender Therapie mit immunmodulatorischen Substanzen.

Selected publications on MS / Ausgewählte Publikationen zum Thema

• Gross CC, Schulte-Mecklenbeck A, Steinberg OV, Wirth T, Lauks S, Bittner S, Schindler P, Baranzini SE, Groppa S, Bellmann-Strobl J, Bünger N, Chien C, Dawin E, Eveslage M, Fleischer V, Gonzalez-Escamilla G, Gisevius B, Haas J, Kerschensteiner M, Kirstein L, Korsukewitz C, Lohmann L, Lünemann JD, Luessi F, Meyer Zu Hörste G, Motte J, Ruck T, Ruprecht K, Schwab N, Steffen F, Meuth SG, Paul F, Wildemann B, Kümpfel T, Gold R, Hahn T, Zipp F, Klotz L, Wiendl H; German Competence Network Multiple Sclerosis (KKNMS). Multiple sclerosis endophenotypes identified by high-dimensional blood signatures are associated with distinct disease trajectories. Sci Transl Med. 2024 Mar 27;16(740):eade8560.
• Foesleitner O, Hayes JC, Weiler M, Sam G, Wildemann B, Wick W, Bendszus M, Heiland S, Jäger LB. Evolution of peripheral nerve changes in early multiple sclerosis-a longitudinal MR neurography study. Front Neurol. 2024 May 3;15:1335408. 
• Foesleitner O, Sturm V, Hayes J, Weiler M, Sam G, Wildemann B, Wick W, Bendszus M, Heiland S, Jäger LB. Microstructural changes of peripheral nerves in early multiple sclerosis: A prospective magnetic resonance neurography study. Eur J Neurol. 2024 Feb;31(2):e16126. 
• Bayas A, Berthele A, Blank N, Dreger P, Faissner S, Friese MA, Gerdes LA, Grauer OM, Häussler V, Heesen C, Janson D, Korporal-Kuhnke M, Kowarik M, Kröger N, Lünemann JD, Martin R, Meier U, Meuth S, Muraro P, Platten M, Schirmer L, Stürner KH, Stellmann JP, Scheid C, Bergh FT, Warnke C, Wildemann B, Ziemssen T. Autologous haematopoietic stem cell transplantation for multiple sclerosis: a position paper and registry outline. Ther Adv Neurol Disord. 2023 Sep 28;16:17562864231180730. 
• Salmen A, Hoepner R, Fleischer V, Heldt M, Gisevius B, Motte J, Ruprecht K, Schneider R, Fisse AL, Grüter T, Lukas C, Berthele A, Giglhuber K, Flaskamp M, Mühlau M, Kirschke J, Bittner S, Groppa S, Lüssi F, Bayas A, Meuth S, Heesen C, Trebst C, Wildemann B, Then Bergh F, Antony G, Kümpfel T, Paul F, Nischwitz S, Tumani H, Zettl U, Hemmer B, Wiendl H, Zipp F, Gold R. Factors associated with depressive mood at the onset of multiple sclerosis - an analysis of 781 patients of the German NationMS cohort. Ther Adv Neurol Disord. 2023 Sep 8;16:17562864231197309.
• Greeck VB, Williams SK, Haas J, Wildemann B, Fairless R. Alterations in lymphocytic metabolism—an emerging hallmark of MS pathophysiology? Int J Mol Sci. 2023 Jan 20;24(3):2094.
• Wildemann B, Jarius S, Lehmann LH, André F, Frey N, Schnitzler P, Jäger L, Gumbinger C, Viehöver A. COVID-19-related severe MS exacerbation with life-threatening Takotsubo cardiomyopathy in a previously stable patient and interference of MS therapy with long-term immunity against SARS-CoV-2. J Neurol 2021 Oct 7:1-4.
• Bayas A, Berthele A, Hemmer B, Warnke C, Wildemann B. Controversy on the treatment of multiple sclerosis and related disorders: positional statement of the expert panel in charge of the 2021 DGN Guideline on diagnosis and treatment of multiple sclerosis, neuromyelitis optica spectrum diseases and MOG-IgG-associated disorders. Neurol Res Pract 2021 Aug 6;3(1):45. doi: 10.1186/s42466-021-00139-8.
• Wick M, Gross CC, Tumani H, Wildemann B, Stangel M, On Behalf Of The German Society Of CSF Diagnostics And Clinical Neurochemistry (DGLN e.V.). Automated Analysis of Cerebrospinal Fluid Cells Using Commercially Available Blood Cell Analysis Devices-A Critical Appraisal. Cells 2021 May 18;10(5):1232. 
• Jarius S, Wilken D, Haas J, Ruprecht K, Komorowski L, Wildemann B. Parvovirus B19 and mumps virus antibodies are major constituents of the intrathecal immune response in European patients with MS and increase the diagnostic sensitivity and discriminatory power of the MRZ reaction. J Neurol. 2021 Mar 26. doi: 10.1007/s00415-021-10471-3; epub ahead of print.
• Pfeuffer S, Ruck T, Pul R, Rolfes L, Korsukewitz C, Pawlitzki M, Wildemann B, Klotz L, Kleinschnitz C, Scalfari A, Wiendl H, Meuth SG. Impact of previous disease-modifying treatment on effectiveness and safety outcomes, among patients with multiple sclerosis treated with alemtuzumab. J Neurol Neurosurg Psychiatry 2021 Sep;92(9):1007-1013.
• Haas J, Rudolph H, Costa L, Faller S, Libicher S, Würthwein C, Jarius S, Ishikawa H, Stump-Guthier C, Tenenbaum T, Schwerk C, Schroten H, Wildemann B. The Choroid Plexus Is Permissive for a Preactivated Antigen-Experienced Memory B-Cell Subset in Multiple Sclerosis. Front Immunol 2021 Jan 26;11:618544.
• 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.
• Gasperi C, Andlauer TFM, Keating A, Knier B, Klein A, Pernpeintner V, Lichtner P, Gold R, Zipp F, Then Bergh F, Stangel M, Tumani H, Wildemann B, Wiendl H, Bayas A, Kümpfel T, Zettl UK, Linker RA, Ziemann U, Knop M, Warnke C, Friese MA, Paul F, Tackenberg B, Berthele A, Hemmer B. Genetic determinants of the humoral immune response in MS. Neurol Neuroimmunol Neuroinflamm. 2020 Jul 16;7(5):e827.
• Simbrich A, Thibaut J, Khil L, Maximov S, Wiendl H, Berger K; REGIMS Investigators. Chances and Challenges of Registry-Based Pharmacovigilance in Multiple Sclerosis: Lessons Learnt from the Implementation of the Multicenter REGIMS Registry. Drug Saf. 2021 Jan;44(1):7-15.
• Butzkueven H, Kappos L, Wiendl H, Trojano M, Spelman T, Chang I, Kasliwal R, Jaitly S, Campbell N, Ho PR, Licata S; Tysabri Observational Program (TOP) Investigators. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). J Neurol Neurosurg Psychiatry. 2020 Jun;91(6):660-668.
• 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.
• Hauser SL, Bar-Or A, Cohen JA, Comi G, Correale J, Coyle PK, Cross AH, de Seze J, Leppert D, Montalban X, Selmaj K, Wiendl H, Kerloeguen C, Willi R, Li B, Kakarieka A, Tomic D, Goodyear A, Pingili R, Häring DA, Ramanathan K, Merschhemke M, Kappos L; ASCLEPIOS I and ASCLEPIOS II Trial Groups. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med. 2020 Aug 6;383(6):546-557.
• Bittner S, Steffen F, Uphaus T, Muthuraman M, Fleischer V, Salmen A, Luessi F, Berthele A, Klotz L, Meuth SG, Bayas A, Paul F, Hartung HP, Linker R, Heesen C, Stangel M, Wildemann B, Then Bergh F, Tackenberg B, Kuempfel T, Weber F, Zettl UK, Ziemann U, Tumani H, Groppa S, Mühlau M, Lukas C, Hemmer B, Wiendl H, Gold R, Zipp F; KKNMS consortium. Clinical implications of serum neurofilament in newly diagnosed MS patients: A longitudinal multicentre cohort study. EBioMedicine. 2020 Jun;56:102807.
• 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.
• Engel S, Graetz C, Salmen A, Muthuraman M, Toenges G, Ambrosius B, Bayas A, Berthele A, Heesen C, Klotz L, Kümpfel T, Linker RA, Meuth SG, Paul F, Stangel M, Tackenberg B, Then Bergh F, Tumani H, Weber F, Wildemann B, Zettl UK, Antony G, Bittner S, Groppa S, Hemmer B, Wiendl H, Gold R, Zipp F, Lill CM, Luessi F; German Competence Network of Multiple Sclerosis. Is APOE ε4 associated with cognitive performance in early MS? Neurol Neuroimmunol Neuroinflamm. 2020 May 1;7(4):e728.
• Tumani H, Petereit HF, Gerritzen A, Gross CC, Huss A, Isenmann S, Jesse S, Khalil M, Lewczuk P, Lewerenz J, Leypoldt F, Melzer N, Meuth SG, Otto M, Ruprecht K, Sindern E, Spreer A, Stangel M, Strik H, Uhr M, Vogelgsang J, Wandinger KP, Weber T, Wick M, Wildemann B, Wiltfang J, Woitalla D, Zerr I, Zimmermann T. S1 guidelines "lumbar puncture and cerebrospinal fluid analysis" (abridged and translated version). Neurol Res Pract. 2020 Mar 16;2:8. 
• Brugnara G, Isensee F, Neuberger U, Bonekamp D, Petersen J, Diem R, Wildemann B, Heiland S, Wick W, Bendszus M, Maier-Hein K, Kickingereder P. Automated volumetric assessment with artificial neural networks might enable a more accurate assessment of disease burden in patients with multiple sclerosis. Eur Radiol. 2020 30(4):2356-2364.
• Haas J, Würthwein C, Korporal-Kuhnke M, Viehoever A, Jarius S, Ruck T, Pfeuffer S, Meuth SG, Wildemann B. Alemtuzumab in Multiple Sclerosis: Short- and Long-Term Effects of Immunodepletion on the Peripheral Treg Compartment. Front Immunol. 2019 Jun 4;10:1204.
• Gasperi C, Salmen A, Antony G, Bayas A, Heesen C, Kümpfel T, Linker RA, Paul F, Stangel M, Tackenberg B, Bergh FT, Warnke C, Weber F, Wiendl H, Wildemann B, Zettl UK, Ziemann U, Zipp F, Tumani H, Gold R, Hemmer B; German Competence Network of Multiple Sclerosis. Association of Intrathecal Immunoglobulin G Synthesis With Disability Worsening in Multiple Sclerosis. JAMA Neurol. 2019 Jul 1;76(7):841-849.
• 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. [Diagnostics and treatment of tuberculosis under immunotherapy for multiple sclerosis : Current status and recommendations in Germany]. Nervenarzt. 2019 Dec;90(12):1245-1253
• Olesen MN, Soelberg K, Debrabant B, Nilsson AC, Lillevang ST, Grauslund J, Brandslund I, Madsen JS, Paul F, Smith TJ, Jarius S, Asgari N. Cerebrospinal fluid biomarkers for predicting development of multiple sclerosis in acute optic neuritis: a population-based prospective cohort study. J Neuroinflammation. 2019 Mar 11;16(1):59. 
• International Multiple Sclerosis Genetics Consortium. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk. Cell. 2019 Jun 27;178(1):262.
• 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.
• Pfeuffer S, Schmidt R, Straeten FA, Pul R, Kleinschnitz C, Wieshuber M, Lee DH, Linker RA, Doerck S, Straeten V, Windhagen S, Pawlitzki M, Aufenberg C, Lang M, Eienbroeker C, Tackenberg B, Limmroth V, Wildemann B, Haas J, Klotz L, Wiendl H, Ruck T, Meuth SG. Efficacy and safety of alemtuzumab versus fingolimod in RRMS after natalizumab cessation. J Neurol. 2019 Jan;266(1):165-173.
• International Multiple Sclerosis Genetics Consortium. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk. Cell. 2018 Nov 29;175(6):1679-1687.e7.
• Karimian-Jazi K, Wildemann B, Diem R, Schwarz D, Hielscher T, Wick W, Bendszus M, Breckwoldt MO. Gd contrast administration is dispensable in patients with MS without new T2 lesions on follow-up MRI. Neurol Neuroimmunol Neuroinflamm. 2018 Jul 16;5(5):e480.
• Kappos L, Bar-Or A, Cree BAC, Fox RJ, Giovannoni G, Gold R, Vermersch P, Arnold DL, Arnould S, Scherz T, Wolf C, Wallström E, Dahlke F; EXPAND Clinical Investigators. Lancet. 2018 Mar 31;391(10127):1263-1273.
• von Bismarck O, Dankowski T, Ambrosius B, Hessler N, Antony G, Ziegler A, Hoshi MM, Aly L, Luessi F, Groppa S, Klotz L, Meuth SG, Tackenberg B, Stoppe M, Then Bergh F, Tumani H, Kümpfel T, Stangel M, Heesen C, Wildemann B, Paul F, Bayas A, Warnke C, Weber F, Linker RA, Ziemann U, Zettl UK, Zipp F, Wiendl H, Hemmer B, Gold R, Salmen A. Treatment choices and neuropsychological symptoms of a large cohort of early MS. Neurol Neuroimmunol Neuroinflamm. 2018 Mar 1;5(3):e446
• Ruprecht K, Wildemann B, Jarius S. The paradoxically low frequency of intrathecal antibody production to Epstein-Barr virus in multiple sclerosis: a structured review of the literature. J Neurol 2017 Nov 2; epub ahead of print (doi: 10.1007/s00415-017-8656-z).
• Jende JME, Hauck GH, Diem R, Weiler M, Heiland S, Wildemann B, Korporal-Kuhnke M, Wick W, Hayes JM, Pfaff J, Pham M, Bendszus M, Kollmer J. Peripheral nerve involvement in multiple sclerosis: Demonstration by magnetic resonance neurography. Ann Neurol. 2017 Nov;82(5):676-685.
• Jarius S, König F, Metz I, Ruprecht K, Paul F, Brück W, Wildemann B. Pattern II and pattern III MS are entities distinct from pattern I MS: evidence from cerebrospinal fluid analysis. J Neuroinflammation 2017 Aug 29; 14:171.
• Hahn S, Trendelenburg G, Scharf M, Denno Y, Brakopp S, Teegen B, Probst C, Wandinger KP, Buttmann M, Haarmann A, Szabados F, Vom Dahl M, Kümpfel T, Eichhorn P, Gold H, Paul F, Jarius S, Melzer N, Stöcker W, Komorowski L. Identification of the flotillin-1/2 heterocomplex as a target of autoantibodies in bona fide multiple sclerosis. J Neuroinflammation 2017 Jun 23;14(1):123.
• Jarius S, Eichhorn P, Franciotta D, Petereit HF, Akman-Demir G, Wick M, Wildemann B. The MRZ reaction as a highly specific marker of multiple sclerosis: re-evaluation and structured review of the literature. J Neurol 2017 Mar;264(3):453-466. [FREE PDF].
• Breckwoldt MO, Gradl J, Hähnel S, Hielscher T, Wildemann B, Diem R, Platten M, Wick W, Heiland S, Bendszus M. Increasing the sensitivity of MRI for the detection of multiple sclerosis lesions by long axial coverage of the spinal cord: a prospective study in 119 patients. J Neurol 2017 Feb;264(2):341-349.
• Haas J, Schwarz A, Korporal-Kuhnke M, Jarius S, Wildemann B. Myeloid Dendritic Cells exhibit Defects in Activation and Function in Patients with Multiple Sclerosis. Journal of Neuroimmunology 2016 Dec 15;301:53-60.
• Schwarz A, Balint B, Korporal-Kuhnke M, Jarius S, von Engelhardt K, Fuerwentsches A, Bussmann C, Ebinger F, Wildemann B*, Haas J*. B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2016 Dec 15;4(1):e309.
• Haas J, Schneider K, Schwarz A, Korporal-Kuhnke M, Faller S, Glehn von F, Jarius S, Wildemann B. Th17 cells: a prognostic marker for MS rebound after natalizumab cessation? Mult Scler 2017 Mar;264(3):453-466.
• Breckwoldt MO, Gradl J, Hähnel S, Hielscher T, Wildemann B, Diem R, Platten M, Wick W, Heiland S, Bendszus M. Increasing the sensitivity of MRI for the detection of multiple sclerosis lesions by long axial coverage of the spinal cord: a prospective study in 119 patients. J Neurol. 2017 Feb;264(2):341-349.
• Biller A, Pflugmann I, Badde S, Diem R, Wildemann B, Nagel AM, Jordan J, Benkhedah N, Kleesiek J. Sodium MRI in Multiple Sclerosis is Compatible with Intracellular Sodium Accumulation and Inflammation-Induced Hyper-Cellularity of Acute Brain Lesions. Sci Rep. 2016 Aug 10;6:31269.
• Huss AM, Halbgebauer S, Öckl P, Trebst C, Spreer A, Borisow N, Harrer A, Brecht I, Balint B, Stich O, Schlegel S, Retzlaff N, Winkelmann A, Roesler R, Lauda F, Yildiz Ö, Voß E, Muche R, Rauer S, Bergh FT, Otto M, Paul F, Wildemann B, Kraus J, Ruprecht K, Stangel M, Buttmann M, Zettl UK, Tumani H. Importance of cerebrospinal fluid analysis in the era of McDonald 2010 criteria: a German-Austrian retrospective multicenter study in patients with a clinically isolated syndrome. J Neurol 2016 Dec;263(12):2499-2504.
• 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.
• Laible M, Jarius S, Mackensen F, Schmidt-Bacher A, Platten M, Haas J, Albrecht P, Wildemann B. Adding papillomacular bundle measurements to standard optical coherence tomography does not increase sensitivity to detect prior optic neuritis in patients with multiple sclerosis. PLoS One 2016 May 12;11(5):e0155322.
• Haas J, Schwarz A, Korporal-Kuhnke M, Faller S, Jarius S, Wildemann B. Hypovitaminosis D upscales B-cell immunoreactivity in multiple sclerosis. J Neuroimmunol 2016 May;294:18–26.
• 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.
• Helling B, König M, Dälken B, Engling A, Krömer W, Heim K, Wallmeier H, Haas J, Wildemann B, Fritz B, Jonuleit H, Kubach J, Dingermann T, Radeke HH, Osterroth F, Uherek C, Czeloth N, Schüttrumpf J. A specific CD4 epitope bound by tregalizumab mediates activation of regulatory T cells by a unique signaling pathway. Immunol Cell Biol 2015 Apr;93(4):396-405.
• Haas J, Schwarz A, Korporal-Kunke M, Jarius S, Wiendl H, Kieseier BC, Wildemann B. Fingolimod does not impair T-cell release from the thymus and beneficially affects Treg function in patients with multiple sclerosis. Mult Scler 2015 Oct;21(12):1521-32.
• Grützke B, Hucke S, Gross CC, Herold MV, Posevitz-Fejfar A, Wildemann BT, Kieseier BC, Dehmel T, Wiendl H, Klotz L. Fingolimod treatment promotes regulatory phenotype and function of B cells. Ann Clin Transl Neurol 2015 Feb;2(2):119-30.
• Kolber P, Luessi F, Meuth SG, Klotz L, Korn T, Trebst C, Tackenberg B, Kieseier B, Kümpfel T, Fleischer V, Tumani H, Wildemann B, Lang M, Flachenecker P, Meier U, Brück W, Limmroth V, Haghikia A, Hartung HP, Stangel M, Hohlfeld R, Hemmer B, Gold R, Wiendl H, Zipp F. [Current aspects of therapy conversion for multiple sclerosis]. Nervenarzt 2015 Oct;86(10):1236-47.
• Balint B, Haas J, Schwarz A, Jarius S, Fürwentsches A, Engelhardt K, Bussmann C, Ebinger F, Fritzsching B, Paul F, Seidel U, Vlaho S, Huppke P, Gärtner J, Wildemann B. T-cell homeostasis in pediatric multiple sclerosis: Old cells in young patients. Neurology 2013;81(9):784-92.
• Schwarz A, Schumacher M, Pfaff D, Schumacher K, Jarius S, Balint B, Wiendl H, Haas J, Wildemann B. Fine-Tuning of Regulatory T Cell Function: The Role of Calcium Signals and Naive Regulatory T Cells for Regulatory T Cell Deficiency in Multiple Sclerosis. J Immunol 2013 May;190(10):4965-70.
• Trinschek B, Luessi F, Haas J, Wildemann B, Zipp F, Wiendl H, Becker C, Jonuleit H. Kinetics of IL-6 production defines T effector cell responsiveness to regulatory T cells in multiple sclerosis. PLOS One 2013 Oct 14;8(10):e77634.
• Schwab N, Schneider-Hohendorf T, Posevitz V, Breuer J, Göbel K, Windhagen S, Brochet B, Vermersch P, Lebrun-Frenay C, Posevitz-Fejfár A, Capra R, Imberti L, Straeten V, Haas J, Wildemann B, Havla J, Kümpfel T, Meinl I, Niessen K, Goelz S, Kleinschnitz C, Warnke C, Buck D, Gold R, Kieseier BC, Meuth SG, Foley J, Chan A, Brassat D, Wiendl H. L-selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients. Neurology. 2013 Sep 3;81(10):865-71.
• Elliott C, Lindner M, Arthur A, Brennan K, Jarius S, Hussey J, Chan A, Stroet A, Tomas Olsson, 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.
• Comi G, Jeffery D, Kappos L, Montalban X, Boyko A, Rocca MA, Filippi M; ALLEGRO Study Group. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med 2012 Mar 15;366(11):1000-9.
• Haas J, Bekeredjian-Ding I, Milkova M, Balint B, Schwarz A, Korporal M, Jarius S, Fritz B, Lorenz HM, Wildemann B. B cells undergo unique compartmentalized redistribution in multiple sclerosis. J Autoimmun 2011 Dec;37(4):289-99.
• Filippi M, Rocca MA, Pagani E, De Stefano N, Jeffery D, Kappos L, Montalban X, Boyko AN, Comi G; ALLEGRO Study Group. Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage. J Neurol Neurosurg Psychiatry. 2014 Aug;85(8):851-8.
• Tumani H, Deisenhammer F, Giovannoni G, Gold R, Hartung HP, Hemmer B, Hohlfeld R, Otto M, Stangel M, Wildemann B, Zettl UK. Revised McDonald criteria: the persisting importance of cerebrospinal fluid analysis. Ann Neurol 2011 Sep;70(3):520.
• Fritzsching B, Haas J, König F, Kunz P, Fritzsching E, Pöschl J, Krammer PH, Brück W, Suri-Payer E, Wildemann B. Intracerebral Human FOXP3+ T Cells: Analysis of CD4+CD25+FOXP3+ T cells in Brain Lesions and Cerebrospinal Fluid of Multiple Sclerosis Patients. PLoS One 2011;18:e17988.
• Haas J, Korporal M, Schwarz A, Balint B and Wildemann B. The interleukin-7 receptor alpha chain contributes to altered homeostasis of regulatory T-cells in multiple sclerosis. Eur J Immunol 2011;41:845-53.
• Haas J, Korporal M, Balint B, Fritzsching B, Schwarz A and Wildemann B. Glatiramer acetate improves regulatory T-cell function by expansion of naive CD4(+)CD25(+)FOXP3(+)CD31(+) T-cells in patients with multiple sclerosis. J Neuroimmunol 2009;216:113-7.
• Multiple Sclerosis Therapy Consensus Group (MSTCG), Wiendl H, Toyka KV, Rieckmann P, Gold R, Hartung HP, Hohlfeld R. Basic and escalating immunomodulatory treatments in multiple sclerosis: current therapeutic recommendations. J Neurol. 2008 Oct;255(10):1449-63.
• Korporal M, Haas J, Balint B, Fritzsching B, Schwarz A, Moeller S, Fritz B, Suri-Payer E and Wildemann B. Interferon beta-induced restoration of regulatory T-cell function in multiple sclerosis is prompted by an increase in newly generated naive regulatory T cells. Arch Neurol 2008;65:1434-9.
• Haas J, Fritzsching B, Trübswetter P, Korporal M, Milkova L, Fritz B, Vobis D, Krammer PH, Suri-Payer E and Wildemann B. Prevalence of Newly Generated Naïve Regulatory T-Cells is Critical for Treg Suppressive Function and Determines Treg Dysfunction in Multiple Sclerosis. J Immunol 2007;179:1322-30.
• Fritzsching B, Korporal M, Haas J, Krammer PH, Suri-Payer E, Wildemann B. Similar sensitivity of regulatory T cells towards CD95L-mediated apoptosis in patients with multiple sclerosis and healthy individuals. J Neurol Sci 2006;251:91-7.
• Haas J, Hug A, Viehöver A, Fritzsching B, Falk CS, Filser A, Vetter T, Milkova L, Korporal M, Fritz B, Storch-Hagenlocher B, Krammer PH, Suri-Payer E, Wildemann B. Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur J Immunol 2005;35:3343-52.
• Fritzsching B, Oberle N, Eberhardt N, Quick S, Haas J, Wildemann B, Krammer PH, Suri-Payer E. In contrast to effector T cells, CD4+CD25+FoxP3+ regulatory T cells are highly susceptible to CD95 ligand- but not to TCR-mediated cell death. J Immunol 2005;175:32-6.
• Hug A, Korporal M, Schröder I, Haas J, Glatz K, Storch-Hagenlocher B, Wildemann B. Thymic export function and T cell homeostasis in patients with relapsing remitting multiple sclerosis. J Immunol 2003;171:432-7.

Awards / Preise

O. Aktas, S. Jarius, C. Trebst, I. Kleiter, M. Krumbholz, U. Hofstadt-van Oy, F. Pache, T. Kümpfel, F. Paul, R. Weissert. Neuromyelitis optica Studiengruppe (NEMOS) 2014: Fortschritte und Herausforderungen bei NMO-Spektrum-Erkrankungen. Jahrestagung der Deutschen Gesellschaft für Neurologie, München, 15.-19. Sept. 2014. Felgenhauer-Preis der DGN.

Helmut-Bauer-Nachwuchspreis für Multiple-Sklerose-Forschung 2013 an Alexander Schwarz für seine Arbeit zu regulatorischen T-Zellen (siehe u.a. Schwarz A, Schumacher M, Pfaff D, Schumacher K, Jarius S, Balint B, Wiendl H, Haas J, Wildemann B. Fine-Tuning of Regulatory T Cell Function: The Role of Calcium Signals and Naive Regulatory T Cells for Regulatory T Cell Deficiency in Multiple Sclerosis. J Immunol 2013 May;190(10):4965-70. PDF)

B. Balint, J. Haas, A. Schwarz, A. Fürwentsches, F. Ebinger, B. Fritzsching, F. Paul, U. Seidel, S. Vlaho, J. Gärtner, B. Wildemann. Pädiatrische Multiple Sklerose: Dysbalance in der T-Zellhomöostase und Dysfunktion regulatorischer T-Zellen. Jahrestagung der Deutschen Gesellschaft für Neurologie, Hamburg, 26.-29. Sept. 2012.

I. Kleiter, P.D. Kraus, O. Grauer, K. Angstwurm, S. Jarius, E. Holler, D. Wolff, W. Schulte-Mattler. Graft-versus-Host Disease-associated Muscle Cramps and Neuropathies in Patients with Allogeneic Hematopoietic Stem Cell Transplantation. Jahrestagung der Deutschen Gesellschaft für Neurologie, Hamburg, 26.-29. Sept. 2012.

M. Korporal, B. Fritz, J. Haas, S. Möller, B. Wildemann. Verbesserung der Hemmkapazität von regulatorischen T-Zellen (CD4+CD25high) bei Patienten mit Multipler Sklerose unter Langzeitbehandlung mit immunmodulatorischen Substanzen. Jahrestagung der Deutschen Gesellschaft für Neurologie, Mannheim, 22.-24. Sept. 2006.

B. Wildemann, E. Suri-Payer , J. Haas, B. Fritzsching, M. Korporal, N. Oberle. Preis der DGN und der Felgenhauer-Stiftung für den Beitrag zum Minisymposium "Regulatorische T-Zellen vom CD4+CD25+Foxp3+ Phänotyp (Treg): Implikationen für Pathogenese und Therapie der Multiplen Sklerose" bei der Neurowoche 2006 in Mannheim