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Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics
Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatiguability of skeletal muscles. It is an antibody-mediated disease, caused by autoantibodies targeting neuromuscular junction proteins. In the majority of patients (~85%) antibodies against the muscle acetylcholi...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033452/ https://www.ncbi.nlm.nih.gov/pubmed/32117321 http://dx.doi.org/10.3389/fimmu.2020.00212 |
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author | Lazaridis, Konstantinos Tzartos, Socrates J. |
author_facet | Lazaridis, Konstantinos Tzartos, Socrates J. |
author_sort | Lazaridis, Konstantinos |
collection | PubMed |
description | Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatiguability of skeletal muscles. It is an antibody-mediated disease, caused by autoantibodies targeting neuromuscular junction proteins. In the majority of patients (~85%) antibodies against the muscle acetylcholine receptor (AChR) are detected, while in 6% antibodies against the muscle-specific kinase (MuSK) are detected. In ~10% of MG patients no autoantibodies can be found with the classical diagnostics for AChR and MuSK antibodies (seronegative MG, SN-MG), making the improvement of methods for the detection of known autoantibodies or the discovery of novel antigenic targets imperative. Over the past years, using cell-based assays or improved highly sensitive immunoprecipitation assays, it has been possible to detect autoantibodies in previously SN-MG patients, including the identification of the low-density lipoprotein receptor-related protein 4 (LRP4) as a third MG autoantigen, as well as AChR and MuSK antibodies undetectable by conventional methods. Furthermore, antibodies against other extracellular or intracellular targets, such as titin, the ryanodine receptor, agrin, collagen Q, K(v)1.4 potassium channels and cortactin have been found in some MG patients, which can be useful biomarkers. In addition to the improvement of diagnosis, the identification of the patients' autoantibody specificity is important for their stratification into respective subgroups, which can differ in terms of clinical manifestations, prognosis and most importantly their response to therapies. The knowledge of the autoantibody profile of MG patients would allow for a therapeutic strategy tailored to their MG subgroup. This is becoming especially relevant as there is increasing progress toward the development of antigen-specific therapies, targeting only the specific autoantibodies or immune cells involved in the autoimmune response, such as antigen-specific immunoadsorption, which have shown promising results. We will herein review the advances made by us and others toward development of more sensitive detection methods and the identification of new antibody targets in MG, and discuss their significance in MG diagnosis and therapy. Overall, the development of novel autoantibody assays is aiding in the more accurate diagnosis and classification of MG patients, supporting the development of advanced therapeutics and ultimately the improvement of disease management and patient quality of life. |
format | Online Article Text |
id | pubmed-7033452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70334522020-02-28 Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics Lazaridis, Konstantinos Tzartos, Socrates J. Front Immunol Immunology Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatiguability of skeletal muscles. It is an antibody-mediated disease, caused by autoantibodies targeting neuromuscular junction proteins. In the majority of patients (~85%) antibodies against the muscle acetylcholine receptor (AChR) are detected, while in 6% antibodies against the muscle-specific kinase (MuSK) are detected. In ~10% of MG patients no autoantibodies can be found with the classical diagnostics for AChR and MuSK antibodies (seronegative MG, SN-MG), making the improvement of methods for the detection of known autoantibodies or the discovery of novel antigenic targets imperative. Over the past years, using cell-based assays or improved highly sensitive immunoprecipitation assays, it has been possible to detect autoantibodies in previously SN-MG patients, including the identification of the low-density lipoprotein receptor-related protein 4 (LRP4) as a third MG autoantigen, as well as AChR and MuSK antibodies undetectable by conventional methods. Furthermore, antibodies against other extracellular or intracellular targets, such as titin, the ryanodine receptor, agrin, collagen Q, K(v)1.4 potassium channels and cortactin have been found in some MG patients, which can be useful biomarkers. In addition to the improvement of diagnosis, the identification of the patients' autoantibody specificity is important for their stratification into respective subgroups, which can differ in terms of clinical manifestations, prognosis and most importantly their response to therapies. The knowledge of the autoantibody profile of MG patients would allow for a therapeutic strategy tailored to their MG subgroup. This is becoming especially relevant as there is increasing progress toward the development of antigen-specific therapies, targeting only the specific autoantibodies or immune cells involved in the autoimmune response, such as antigen-specific immunoadsorption, which have shown promising results. We will herein review the advances made by us and others toward development of more sensitive detection methods and the identification of new antibody targets in MG, and discuss their significance in MG diagnosis and therapy. Overall, the development of novel autoantibody assays is aiding in the more accurate diagnosis and classification of MG patients, supporting the development of advanced therapeutics and ultimately the improvement of disease management and patient quality of life. Frontiers Media S.A. 2020-02-14 /pmc/articles/PMC7033452/ /pubmed/32117321 http://dx.doi.org/10.3389/fimmu.2020.00212 Text en Copyright © 2020 Lazaridis and Tzartos. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Lazaridis, Konstantinos Tzartos, Socrates J. Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics |
title | Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics |
title_full | Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics |
title_fullStr | Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics |
title_full_unstemmed | Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics |
title_short | Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics |
title_sort | autoantibody specificities in myasthenia gravis; implications for improved diagnostics and therapeutics |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033452/ https://www.ncbi.nlm.nih.gov/pubmed/32117321 http://dx.doi.org/10.3389/fimmu.2020.00212 |
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