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Profiling Serum Antibodies Against Muscle Antigens in Facioscapulohumeral Muscular Dystrophy Finds No Disease-Specific Autoantibodies
BACKGROUND: FSHD is caused by specific genetic mutations resulting in activation of the Double Homeobox 4 gene (DUX4). DUX4 targets hundreds of downstream genes eventually leading to muscle atrophy, oxidative stress, abnormal myogenesis, and muscle inflammation. We hypothesized that DUX4-induced abe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9789485/ https://www.ncbi.nlm.nih.gov/pubmed/34024774 http://dx.doi.org/10.3233/JND-210653 |
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author | Greco, Anna Straasheijm, Kirsten R. Mul, Karlien van den Heuvel, Anita van der Maarel, Silvère M. Joosten, Leo A.B. van Engelen, Baziel G.M. Pruijn, Ger J.M. |
author_facet | Greco, Anna Straasheijm, Kirsten R. Mul, Karlien van den Heuvel, Anita van der Maarel, Silvère M. Joosten, Leo A.B. van Engelen, Baziel G.M. Pruijn, Ger J.M. |
author_sort | Greco, Anna |
collection | PubMed |
description | BACKGROUND: FSHD is caused by specific genetic mutations resulting in activation of the Double Homeobox 4 gene (DUX4). DUX4 targets hundreds of downstream genes eventually leading to muscle atrophy, oxidative stress, abnormal myogenesis, and muscle inflammation. We hypothesized that DUX4-induced aberrant expression of genes triggers a sustained autoimmune response against skeletal muscle cells. OBJECTIVE: This study aimed at the identification of autoantibodies directed against muscle antigens in FSHD. Moreover, a possible relationship between serum antibody reactivity and DUX4 expression was also investigated. METHODS: FSHD sera (N = 138, 48±16 years, 48% male) and healthy control sera (N = 20, 47±14 years, 50% male) were analyzed by immunoblotting for antibodies against several skeletal muscle protein extracts: healthy muscle, FSHD muscle, healthy and FSHD myotubes, and inducible DUX4 expressing myoblasts. In addition, DUX4 expressing myoblasts were analyzed by immunofluorescence with FSHD and healthy control sera. RESULTS: The results showed that the reactivity of FSHD sera did not significantly differ from that of healthy controls, with all the tested muscle antigen extracts. Besides, the immunofluorescent staining of DUX4-expressing myoblasts was not different when incubated with either FSHD or healthy control sera. CONCLUSION: Since the methodology used did not lead to the identification of disease-specific autoantibodies in the FSHD cohort, we suggest that autoantibody-mediated pathology may not be an important disease mechanism in FSHD. Nevertheless, it is crucial to further unravel if and which role the immune system plays in FSHD pathogenesis. Other innate as well as adaptive immune players could be involved in the complex DUX4 cascade of events and could become appealing druggable targets. |
format | Online Article Text |
id | pubmed-9789485 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-97894852023-01-17 Profiling Serum Antibodies Against Muscle Antigens in Facioscapulohumeral Muscular Dystrophy Finds No Disease-Specific Autoantibodies Greco, Anna Straasheijm, Kirsten R. Mul, Karlien van den Heuvel, Anita van der Maarel, Silvère M. Joosten, Leo A.B. van Engelen, Baziel G.M. Pruijn, Ger J.M. J Neuromuscul Dis Research Report BACKGROUND: FSHD is caused by specific genetic mutations resulting in activation of the Double Homeobox 4 gene (DUX4). DUX4 targets hundreds of downstream genes eventually leading to muscle atrophy, oxidative stress, abnormal myogenesis, and muscle inflammation. We hypothesized that DUX4-induced aberrant expression of genes triggers a sustained autoimmune response against skeletal muscle cells. OBJECTIVE: This study aimed at the identification of autoantibodies directed against muscle antigens in FSHD. Moreover, a possible relationship between serum antibody reactivity and DUX4 expression was also investigated. METHODS: FSHD sera (N = 138, 48±16 years, 48% male) and healthy control sera (N = 20, 47±14 years, 50% male) were analyzed by immunoblotting for antibodies against several skeletal muscle protein extracts: healthy muscle, FSHD muscle, healthy and FSHD myotubes, and inducible DUX4 expressing myoblasts. In addition, DUX4 expressing myoblasts were analyzed by immunofluorescence with FSHD and healthy control sera. RESULTS: The results showed that the reactivity of FSHD sera did not significantly differ from that of healthy controls, with all the tested muscle antigen extracts. Besides, the immunofluorescent staining of DUX4-expressing myoblasts was not different when incubated with either FSHD or healthy control sera. CONCLUSION: Since the methodology used did not lead to the identification of disease-specific autoantibodies in the FSHD cohort, we suggest that autoantibody-mediated pathology may not be an important disease mechanism in FSHD. Nevertheless, it is crucial to further unravel if and which role the immune system plays in FSHD pathogenesis. Other innate as well as adaptive immune players could be involved in the complex DUX4 cascade of events and could become appealing druggable targets. IOS Press 2021-09-14 /pmc/articles/PMC9789485/ /pubmed/34024774 http://dx.doi.org/10.3233/JND-210653 Text en © 2021 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Report Greco, Anna Straasheijm, Kirsten R. Mul, Karlien van den Heuvel, Anita van der Maarel, Silvère M. Joosten, Leo A.B. van Engelen, Baziel G.M. Pruijn, Ger J.M. Profiling Serum Antibodies Against Muscle Antigens in Facioscapulohumeral Muscular Dystrophy Finds No Disease-Specific Autoantibodies |
title | Profiling Serum Antibodies Against Muscle Antigens in Facioscapulohumeral Muscular Dystrophy Finds No Disease-Specific Autoantibodies |
title_full | Profiling Serum Antibodies Against Muscle Antigens in Facioscapulohumeral Muscular Dystrophy Finds No Disease-Specific Autoantibodies |
title_fullStr | Profiling Serum Antibodies Against Muscle Antigens in Facioscapulohumeral Muscular Dystrophy Finds No Disease-Specific Autoantibodies |
title_full_unstemmed | Profiling Serum Antibodies Against Muscle Antigens in Facioscapulohumeral Muscular Dystrophy Finds No Disease-Specific Autoantibodies |
title_short | Profiling Serum Antibodies Against Muscle Antigens in Facioscapulohumeral Muscular Dystrophy Finds No Disease-Specific Autoantibodies |
title_sort | profiling serum antibodies against muscle antigens in facioscapulohumeral muscular dystrophy finds no disease-specific autoantibodies |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9789485/ https://www.ncbi.nlm.nih.gov/pubmed/34024774 http://dx.doi.org/10.3233/JND-210653 |
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