Cargando…

Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis

Myasthenia gravis (MG) is a neuromuscular autoimmune disease characterized by prevalence in young women (3:1). Several mechanisms proposed as explanations for gender bias, including skewed X chromosome inactivation (XCI) and dosage or sex hormones, are often involved in the development of autoimmuni...

Descripción completa

Detalles Bibliográficos
Autores principales: Nicolì, Vanessa, Tabano, Silvia Maria, Colapietro, Patrizia, Maestri, Michelangelo, Ricciardi, Roberta, Stoccoro, Andrea, Fontana, Laura, Guida, Melania, Miozzo, Monica, Coppedè, Fabio, Migliore, Lucia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031138/
https://www.ncbi.nlm.nih.gov/pubmed/35456502
http://dx.doi.org/10.3390/genes13040696
_version_ 1784692315381563392
author Nicolì, Vanessa
Tabano, Silvia Maria
Colapietro, Patrizia
Maestri, Michelangelo
Ricciardi, Roberta
Stoccoro, Andrea
Fontana, Laura
Guida, Melania
Miozzo, Monica
Coppedè, Fabio
Migliore, Lucia
author_facet Nicolì, Vanessa
Tabano, Silvia Maria
Colapietro, Patrizia
Maestri, Michelangelo
Ricciardi, Roberta
Stoccoro, Andrea
Fontana, Laura
Guida, Melania
Miozzo, Monica
Coppedè, Fabio
Migliore, Lucia
author_sort Nicolì, Vanessa
collection PubMed
description Myasthenia gravis (MG) is a neuromuscular autoimmune disease characterized by prevalence in young women (3:1). Several mechanisms proposed as explanations for gender bias, including skewed X chromosome inactivation (XCI) and dosage or sex hormones, are often involved in the development of autoimmunity. The skewed XCI pattern can lead to an unbalanced expression of some X-linked genes, as observed in several autoimmune disorders characterized by female predominance. No data are yet available regarding XCI and MG. We hypothesize that the preferential XCI pattern may contribute to the female bias observed in the onset of MG, especially among younger women. XCI analysis was performed on blood samples of 284 women between the ages of 20 and 82. XCI was tested using the Human Androgen Receptor Assay (HUMARA). XCI patterns were classified as random (XCI < 75%) and preferential (XCI ≥ 75%). In 121 informative patients, the frequency of skewed XCI patterns was 47%, significantly higher than in healthy controls (17%; p ≤ 0.00001). Interestingly, the phenomenon was observed mainly in younger patients (<45 years; p ≤ 0.00001). Furthermore, considering the XCI pattern and the other clinical characteristics of patients, no significant differences were found. In conclusion, we observed preferential XCI in MG female patients, suggesting its potential role in the aetiology of MG, as observed in other autoimmune diseases in women.
format Online
Article
Text
id pubmed-9031138
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90311382022-04-23 Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis Nicolì, Vanessa Tabano, Silvia Maria Colapietro, Patrizia Maestri, Michelangelo Ricciardi, Roberta Stoccoro, Andrea Fontana, Laura Guida, Melania Miozzo, Monica Coppedè, Fabio Migliore, Lucia Genes (Basel) Article Myasthenia gravis (MG) is a neuromuscular autoimmune disease characterized by prevalence in young women (3:1). Several mechanisms proposed as explanations for gender bias, including skewed X chromosome inactivation (XCI) and dosage or sex hormones, are often involved in the development of autoimmunity. The skewed XCI pattern can lead to an unbalanced expression of some X-linked genes, as observed in several autoimmune disorders characterized by female predominance. No data are yet available regarding XCI and MG. We hypothesize that the preferential XCI pattern may contribute to the female bias observed in the onset of MG, especially among younger women. XCI analysis was performed on blood samples of 284 women between the ages of 20 and 82. XCI was tested using the Human Androgen Receptor Assay (HUMARA). XCI patterns were classified as random (XCI < 75%) and preferential (XCI ≥ 75%). In 121 informative patients, the frequency of skewed XCI patterns was 47%, significantly higher than in healthy controls (17%; p ≤ 0.00001). Interestingly, the phenomenon was observed mainly in younger patients (<45 years; p ≤ 0.00001). Furthermore, considering the XCI pattern and the other clinical characteristics of patients, no significant differences were found. In conclusion, we observed preferential XCI in MG female patients, suggesting its potential role in the aetiology of MG, as observed in other autoimmune diseases in women. MDPI 2022-04-15 /pmc/articles/PMC9031138/ /pubmed/35456502 http://dx.doi.org/10.3390/genes13040696 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nicolì, Vanessa
Tabano, Silvia Maria
Colapietro, Patrizia
Maestri, Michelangelo
Ricciardi, Roberta
Stoccoro, Andrea
Fontana, Laura
Guida, Melania
Miozzo, Monica
Coppedè, Fabio
Migliore, Lucia
Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis
title Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis
title_full Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis
title_fullStr Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis
title_full_unstemmed Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis
title_short Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis
title_sort preferential x chromosome inactivation as a mechanism to explain female preponderance in myasthenia gravis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031138/
https://www.ncbi.nlm.nih.gov/pubmed/35456502
http://dx.doi.org/10.3390/genes13040696
work_keys_str_mv AT nicolivanessa preferentialxchromosomeinactivationasamechanismtoexplainfemalepreponderanceinmyastheniagravis
AT tabanosilviamaria preferentialxchromosomeinactivationasamechanismtoexplainfemalepreponderanceinmyastheniagravis
AT colapietropatrizia preferentialxchromosomeinactivationasamechanismtoexplainfemalepreponderanceinmyastheniagravis
AT maestrimichelangelo preferentialxchromosomeinactivationasamechanismtoexplainfemalepreponderanceinmyastheniagravis
AT ricciardiroberta preferentialxchromosomeinactivationasamechanismtoexplainfemalepreponderanceinmyastheniagravis
AT stoccoroandrea preferentialxchromosomeinactivationasamechanismtoexplainfemalepreponderanceinmyastheniagravis
AT fontanalaura preferentialxchromosomeinactivationasamechanismtoexplainfemalepreponderanceinmyastheniagravis
AT guidamelania preferentialxchromosomeinactivationasamechanismtoexplainfemalepreponderanceinmyastheniagravis
AT miozzomonica preferentialxchromosomeinactivationasamechanismtoexplainfemalepreponderanceinmyastheniagravis
AT coppedefabio preferentialxchromosomeinactivationasamechanismtoexplainfemalepreponderanceinmyastheniagravis
AT migliorelucia preferentialxchromosomeinactivationasamechanismtoexplainfemalepreponderanceinmyastheniagravis