title: Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles.
abstract: OBJECTIVE
  We aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab.
  
  
  METHODS
  HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration.
  
  
  RESULTS
  A total of 119 patients with MS from 3 different cohorts were included in the study: 54 with natalizumab-related anaphylactic/anaphylactoid reactions and 65 without allergic reactions. HLA-DRB1*13 and HLA-DRB1*14 alleles were significantly increased in patients who developed anaphylactic/anaphylactoid reactions (p M-H = 3 × 10(-7); odds ratio [OR]M-H = 8.96, 95% confidence interval [CI] = 3.40-23.64), with a positive predictive value (PPV) of 82%. In contrast, the HLA-DRB1*15 allele was significantly more represented in patients who did not develop anaphylactic/anaphylactoid reactions to natalizumab (p M-H = 6 × 10(-4); ORM-H = 0.2, 95% CI = 0.08-0.50), with a PPV of 81%.
  
  
  CONCLUSIONS
  HLA-DRB1 genotyping before natalizumab treatment may help neurologists to identify patients with MS at risk for developing serious systemic hypersensitivity reactions associated with natalizumab administration.
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: de la Hera
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Brassat
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chan
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Vidal-Jordana
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Anke
authors.initials: A
authors.lastname: Salmen
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Luisa Maria
authors.initials: LM
authors.lastname: Villar
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Alvarez-Cermeño
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernández
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Oliver
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Saiz
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Jose Ramón
authors.initials: JR
authors.lastname: Ara
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Ana G
authors.initials: AG
authors.lastname: Vigo
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Meca
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Sunny
authors.initials: S
authors.lastname: Malhotra
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Fissolo
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Horga
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.affiliation: Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., 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, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella