Restoring immune tolerance in neuromyelitis optica Part I

Larry Steinman, Amit Bar-Or, Jacinta M. Behne, Daniel Benitez-Ribas, Peter S. Chin, Michael Clare-Salzler, Donald Healey, James I. Kim, David M. Kranz, Andreas Lutterotti, Roland Martin, Sven Schippling, Pablo Villoslada, Cheng Hong Wei, Howard L. Weiner, Scott S. Zamvil, Michael R. Yeaman, Terry J. Smith

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Article numbere276
JournalNeurology: Neuroimmunology and NeuroInflammation
Issue number5
StatePublished - 2016

ASJC Scopus subject areas

  • Medicine(all)


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