title: Restoring immune tolerance in neuromyelitis optica: Part I.
abstract: Neuromyelitis optica (NMO) and spectrum disorder (NMO/SD) represent a vexing process and its clinical variants appear to have at their pathogenic core the loss of immune tolerance to the aquaporin-4 water channel protein. This process results in a characteristic pattern of astrocyte dysfunction, loss, and demyelination that predominantly affects the spinal cord and optic nerves. Although several empirical therapies are currently used in the treatment of NMO/SD, none has been proven effective in prospective, adequately powered, randomized trials. Furthermore, most of the current therapies subject patients to long-term immunologic suppression that can cause serious infections and development of cancers. The following is the first of a 2-part description of several key immune mechanisms in NMO/SD that might be amenable to therapeutic restoration of immune tolerance. It is intended to provide a roadmap for how potential immune tolerance restorative techniques might be applied to patients with NMO/SD. This initial installment provides a background rationale underlying attempts at immune tolerization. It provides specific examples of innovative approaches that have emerged recently as a consequence of technical advances. In several autoimmune diseases, these strategies have been reduced to practice. Therefore, in theory, the identification of aquaporin-4 as the dominant autoantigen makes NMO/SD an ideal candidate for the development of tolerizing therapies or cures for this increasingly recognized disease.
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Larry
authors.initials: L
authors.lastname: Steinman
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Jacinta M
authors.initials: JM
authors.lastname: Behne
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Benitez-Ribas
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Peter S
authors.initials: PS
authors.lastname: Chin
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Michael
authors.initials: M
authors.lastname: Clare-Salzler
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Donald
authors.initials: D
authors.lastname: Healey
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: James I
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: David M
authors.initials: DM
authors.lastname: Kranz
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Andreas
authors.initials: A
authors.lastname: Lutterotti
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Sven
authors.initials: S
authors.lastname: Schippling
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Pablo
authors.initials: P
authors.lastname: Villoslada
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Wei
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Scott S
authors.initials: SS
authors.lastname: Zamvil
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Michael R
authors.initials: MR
authors.lastname: Yeaman
authors.affiliation: Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; The Guthy-Jackson Charitable Foundation (J.M.B.), San Diego, CA; Department of Gastroenterology (D.B.-R., P.V.), Hospital Clínic, CIBERehd and Center of Neuroimmunology & Inflammatory Bowel Disease, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Genentech, Inc. (P.S.C.), South San Francisco, CA; Department of Pathology (M.C.-S.), University of Florida School of Medicine, Gainesville; Opexa Therapeutics (D.H.), The Woodlands, TX; Department of Surgery (J.I.K.), Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Biochemistry (D.M.K.), University of Illinois, Urbana; Neuroimmunology and MS Research (A.L., R.M., S.S.), Department of Neurology, University Hospital Zurich, University Zurich, Switzerland; Forest Landing Court (H.L.W.), Rockville, MD; Ann Romney Center for Neurologic Diseases (S.S.Z.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (H.L.W.), University of California, San Francisco School of Medicine; Department of Medicine (S.S.Z.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Division of Metabolism and Endocrine Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor (T.J.S.).
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Smith