Restoring immune tolerance in neuromyelitis optica Part II

Amit Bar-Or, Larry Steinman, 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, Terry J. Smith, Michael R. Yeaman

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere277
JournalNeurology: Neuroimmunology and NeuroInflammation
Volume3
Issue number5
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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