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The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders

An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins and associate with highly specific phenotypes, suggesting they have pathogenic potential. Below, we describe the phenotypes associa...

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Autores principales: Damato, Valentina, Balint, Bettina, Kienzler, Anne‐Kathrin, Irani, Sarosh R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221172/
https://www.ncbi.nlm.nih.gov/pubmed/30218501
http://dx.doi.org/10.1002/mds.27446
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author Damato, Valentina
Balint, Bettina
Kienzler, Anne‐Kathrin
Irani, Sarosh R.
author_facet Damato, Valentina
Balint, Bettina
Kienzler, Anne‐Kathrin
Irani, Sarosh R.
author_sort Damato, Valentina
collection PubMed
description An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins and associate with highly specific phenotypes, suggesting they have pathogenic potential. Below, we describe the phenotypes associated with some of these commoner autoantibody‐mediated movement disorders, and outline increasingly well‐established mechanisms of autoantibody pathogenicity which include antigen downregulation and complement fixation. Despite these advances, and the increasingly robust evidence for improved clinical outcomes with early escalation of immunotherapies, the underlying cellular immunology of these conditions has received little attention. Therefore, here, we outline the likely roles of T cells and B cells in the generation of autoantibodies, and reflect on how these may guide both current immunotherapy regimes and our future understanding of precision medicine in the field. In addition, we summarise potential mechanisms by which these peripherally‐driven immune responses may reach the central nervous system. We integrate this with the immunologically‐relevant clinical observations of preceding infections, tumours and human leucocyte antigen‐associations to provide an overview of the therapeutically‐relevant underlying adaptive immunology in the autoantibody‐mediated movement disorders. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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spelling pubmed-62211722018-11-15 The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders Damato, Valentina Balint, Bettina Kienzler, Anne‐Kathrin Irani, Sarosh R. Mov Disord Reviews An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins and associate with highly specific phenotypes, suggesting they have pathogenic potential. Below, we describe the phenotypes associated with some of these commoner autoantibody‐mediated movement disorders, and outline increasingly well‐established mechanisms of autoantibody pathogenicity which include antigen downregulation and complement fixation. Despite these advances, and the increasingly robust evidence for improved clinical outcomes with early escalation of immunotherapies, the underlying cellular immunology of these conditions has received little attention. Therefore, here, we outline the likely roles of T cells and B cells in the generation of autoantibodies, and reflect on how these may guide both current immunotherapy regimes and our future understanding of precision medicine in the field. In addition, we summarise potential mechanisms by which these peripherally‐driven immune responses may reach the central nervous system. We integrate this with the immunologically‐relevant clinical observations of preceding infections, tumours and human leucocyte antigen‐associations to provide an overview of the therapeutically‐relevant underlying adaptive immunology in the autoantibody‐mediated movement disorders. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. John Wiley and Sons Inc. 2018-09-14 2018-09 /pmc/articles/PMC6221172/ /pubmed/30218501 http://dx.doi.org/10.1002/mds.27446 Text en © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reviews
Damato, Valentina
Balint, Bettina
Kienzler, Anne‐Kathrin
Irani, Sarosh R.
The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders
title The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders
title_full The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders
title_fullStr The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders
title_full_unstemmed The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders
title_short The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders
title_sort clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221172/
https://www.ncbi.nlm.nih.gov/pubmed/30218501
http://dx.doi.org/10.1002/mds.27446
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