Neuroimmunology 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.
Neurol Neuroimmunol Neuroinflamm. 2016 Sep 7;3(5):e277. doi: 10.1212/NXI.0000000000000277. eCollection 2016 Oct.
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.
视神经脊髓炎谱系疾病（NMO/SD）及其临床变异以对水通道蛋白-4（AQP4）和其他自身抗原失去免疫耐受为核心。其特征表型是星形胶质细胞功能障碍和脊髓、视神经以及特定脑区脱髓鞘。在这篇由两部分组成的文章的第二部分中，我们进一步提出了关于 NMO/SD 发病机制的观点，以及如何利用新兴技术来恢复对疾病相关自身抗原的免疫耐受。NMO/SD 似乎特别适合这些策略，因为已经确定 AQP4 是主要的自身抗原。最近在疾病的实验模型和人类中重新引入免疫耐受的技术进步，应该会鼓励该领域取得飞跃式发展，从而为新疗法提供可能。在本系列文章的这一部分，重点介绍了调节性 T 和 B 细胞的潜力，以及口服耐受的新方法。最后，提供了一张路线图，以帮助识别临床开发中的潜在问题，并指导耐受治疗在通过新兴技术解决 NMO/SD 方面的应用。这些观点都旨在为 NMO/SD 和其他自身免疫性疾病提供新的治疗方法，同时避免对正常宿主防御机制的影响。
