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Induction of Paralysis and Visual System Injury in Mice by T Cells Specific for Neuromyelitis Optica Autoantigen Aquaporin-4
Published on: August 21, 2017
Restoring immune tolerance in neuromyelitis optica: Part II
Amit Bar-Or1, Larry Steinman1, Jacinta M Behne1
1Neuroimmunology Unit and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto; 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, 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; Ann Romney Center for Neurologic Diseases (H.L.W.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology and Program in Immunology (S.S.Z.), University of California, San Francisco School of Medicine; Department of Ophthalmology and Visual Sciences (T.J.S.), Kellogg Eye Center, and Division of Metabolism, Endocrine and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor; Department of Medicine (M.R.Y.), Divisions of Molecular Medicine & Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles; and Harbor-UCLA Medical Center & LABioMed at Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA.
Abstract:
Neuromyelitis optica spectrum disorder (NMO/SD) and its clinical variants have at their core the loss of immune tolerance to aquaporin-4 and perhaps other autoantigens. The characteristic phenotype is disruption of astrocyte function and demyelination of spinal cord, optic nerves, and particular brain regions. In this second of a 2-part article, we present further perspectives regarding the pathogenesis of NMO/SD and how this disease might be amenable to emerging technologies aimed at restoring immune tolerance to disease-implicated self-antigens. NMO/SD appears to be particularly well-suited for these strategies since aquaporin-4 has already been identified as the dominant autoantigen. The recent technical advances in reintroducing immune tolerance in experimental models of disease as well as in humans should encourage quantum leaps in this area that may prove productive for novel therapy. In this part of the article series, the potential for regulatory T and B cells is brought into focus, as are new approaches to oral tolerization. Finally, a roadmap is provided to help identify potential issues in clinical development and guide applications in tolerization therapy to solving NMO/SD through the use of emerging technologies. Each of these perspectives is intended to shine new light on potential cures for NMO/SD and other autoimmune diseases, while sparing normal host defense mechanisms.
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