Restoring immune tolerance in neuromyelitis optica: Part I. Issue 5 (October 2016)

• Record Type: Journal Article
• Authors: Steinman, Larry; Bar-Or, Amit; Behne, Jacinta M.; Benitez-Ribas, Daniel; Chin, Peter S.; Clare-Salzler, Michael; Healey, Donald; Kim, James I.; Kranz, David M.; Lutterotti, Andreas; Martin, Roland; Schippling, Sven; Villoslada, Pablo; Wei, Cheng-Hong; Weiner, Howard L.; Zamvil, Scott S.; Yeaman, Michael R.; Smith, Terry J.; Aktas, Orhan; Amezcua, Lilyana; Appiwatanakul, Metha; Asgari, Nasrin; Banwell, Brenda; Bennett, Jeffrey; Bowen, James; Cabre, Philippe; Chitnis, Tanuja; Cohen, Jeffrey; De Seze, Jerome; Fujihara, Kazuo; Han, May; Hellwig, Kerstin; Hintzen, Rogier; Hooper, D. Craig; Iorio, Raffaele; Jacob, Anu; Jarius, Sven; Kim, Ho Jin; Kissani, Najib; Klawiter, Eric C.; Kleiter, Ingo; Lana-Peixoto, Marco; Leite, Maria Isabel; Levy, Michael; Lublin, Fred; Draayer, Yang Mao; Marignier, Romain; Matiello, Marcelo; Nakashima, Ichiro; O'Connor, Kevin C.; Palace, Jacqueline; Pandit, Lekha; Paul, Friedemann; Prayoonwiwat, Naraporn; Riley, Claire; Ruprecht, Klemens; Saiz, Albert; Siritho, Sasitorn; Tenembaum, Silvia; Weinshenker, Brian; Wingerchuk, Dean; Würfel, Jens;
• Is Part Of: Neurology. Volume 3:Issue 5(2016)
• Publication Date: 2016-10
• Subjects: Neuroimmunology -- Periodicals; Neurology -- Periodicals; 616.8
• DOI: 10.1212/NXI.0000000000000276
• Languages: English
• ISSNs: 2332-7812

Abstract

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.