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Restoring immune tolerance in neuromyelitis optica: Part II


Bar-Or, A; Steinman, L; Behne, J M; Benitez-Ribas, D; Chin, P S; Clare-Salzler, M; Healey, D; Kim, J I; Kranz, D M; Lutterotti, A; Martin, R; Schippling, S; Villoslada, P; Wei, C H; Weiner, H L; Zamvil, S S; Smith, T J; Yeaman, M R (2016). Restoring immune tolerance in neuromyelitis optica: Part II. Neurology: Neuroimmunology and Neuroinflammation, 3(5):e277.

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.

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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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:October 2016
Deposited On:18 Nov 2016 07:50
Last Modified:04 Aug 2017 15:39
Publisher:American Academy of Neurology
ISSN:2332-7812
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1212/NXI.0000000000000277
Related URLs:http://www.zora.uzh.ch/127661/
PubMed ID:27648464

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