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Lunemann JD, Hegen H, Villar LM, Rejdak K, Sao-Aviles A, Carbonell-Mirabent P, Sastre-Garriga J, Mongay-Ochoa N, Berek K, Martínez-Yélamos S, Pérez-Miralles F, Abdelhak A, Bachhuber F, Tumani H, Lycke JN, Rosenstein I, Alvarez-Lafuente R, Castillo-Trivino T, Otaegui D, Llufriu S, Blanco Y, Sánchez López AJ, Garcia Merino JA, Fissolo N, Gutierrez L, Villacieros-Álvarez J, Monreal E, Valls-Carbó A, Wiendl H, Montalban X, Comabella M. Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis. NEUROLOGY(R) NEUROIMMUNOLOGY & NEUROINFLAMMATION 2024; 11:e200270. [PMID: 38912898 PMCID: PMC11226316 DOI: 10.1212/nxi.0000000000200270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 04/26/2024] [Indexed: 06/25/2024]
Abstract
BACKGROUND AND OBJECTIVES The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS). METHODS Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up). RESULTS In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; p = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; p = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; p = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; p = 0.025). DISCUSSION Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.
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Affiliation(s)
- Jan D Lunemann
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Harald Hegen
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Luisa María Villar
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Konrad Rejdak
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Augusto Sao-Aviles
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Pere Carbonell-Mirabent
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Jaume Sastre-Garriga
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Neus Mongay-Ochoa
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Klaus Berek
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Sergio Martínez-Yélamos
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Francisco Pérez-Miralles
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Ahmed Abdelhak
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Franziska Bachhuber
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Hayrettin Tumani
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Jan N Lycke
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Igal Rosenstein
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Roberto Alvarez-Lafuente
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Tamara Castillo-Trivino
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - David Otaegui
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Sara Llufriu
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Yolanda Blanco
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Antonio J Sánchez López
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Juan Antonio Garcia Merino
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Nicolas Fissolo
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Lucia Gutierrez
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Javier Villacieros-Álvarez
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Enric Monreal
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Adrián Valls-Carbó
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Heinz Wiendl
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Xavier Montalban
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
| | - Manuel Comabella
- From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain
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