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Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers
X-linked Granulomatous Disease (XL-CGD) carriers were previously thought to be clinically healthy because random X-chromosome inactivation (XCI) allows approximately half of their phagocytes/monocytes to express functional gp91phox protein. This supports the NADPH oxidase activity necessary for the...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229314/ https://www.ncbi.nlm.nih.gov/pubmed/34206017 http://dx.doi.org/10.3390/antiox10060891 |
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author | Chiriaco, Maria Salfa, Irene Ursu, Giorgiana Madalina Cifaldi, Cristina Di Cesare, Silvia Rossi, Paolo Di Matteo, Gigliola Finocchi, Andrea |
author_facet | Chiriaco, Maria Salfa, Irene Ursu, Giorgiana Madalina Cifaldi, Cristina Di Cesare, Silvia Rossi, Paolo Di Matteo, Gigliola Finocchi, Andrea |
author_sort | Chiriaco, Maria |
collection | PubMed |
description | X-linked Granulomatous Disease (XL-CGD) carriers were previously thought to be clinically healthy because random X-chromosome inactivation (XCI) allows approximately half of their phagocytes/monocytes to express functional gp91phox protein. This supports the NADPH oxidase activity necessary for the killing of engulfed pathogens. Some XL-CGD carriers suffer from inflammatory and autoimmune manifestations as well as infections, although the skewed-XCI of a mutated allele is reported to be exclusively determinant for infection susceptibility. Indeed, immune dysregulation could be determined by dysfunctional non-phagocytic leukocytes rather than the percentage of functioning neutrophils. Here we investigated in a cohort of 12 X-CGD female carriers at a particular time of their life the gp91phox protein expression/function and how this affects immune cell function. We showed that 50% of carriers have an age-independent skewed-XCI and 65% of them have a misrepresented expression of the wild-type gene. The majority of carriers manifested immune dysregulation and GI manifestations regardless of age and XCI. Immunological investigations revealed an increase in CD19+ B cells, CD56bright-NK cell percentage, a slightly altered CD107a upregulation on CD4+ T cells, and reduced INFγ-production by CD4+ and CD8+ cells. Notably, we demonstrated that the residual level of ROS robustly correlates with INFγ-expressing T cells, suggesting a role in promoting immune dysregulation in carriers. |
format | Online Article Text |
id | pubmed-8229314 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82293142021-06-26 Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers Chiriaco, Maria Salfa, Irene Ursu, Giorgiana Madalina Cifaldi, Cristina Di Cesare, Silvia Rossi, Paolo Di Matteo, Gigliola Finocchi, Andrea Antioxidants (Basel) Article X-linked Granulomatous Disease (XL-CGD) carriers were previously thought to be clinically healthy because random X-chromosome inactivation (XCI) allows approximately half of their phagocytes/monocytes to express functional gp91phox protein. This supports the NADPH oxidase activity necessary for the killing of engulfed pathogens. Some XL-CGD carriers suffer from inflammatory and autoimmune manifestations as well as infections, although the skewed-XCI of a mutated allele is reported to be exclusively determinant for infection susceptibility. Indeed, immune dysregulation could be determined by dysfunctional non-phagocytic leukocytes rather than the percentage of functioning neutrophils. Here we investigated in a cohort of 12 X-CGD female carriers at a particular time of their life the gp91phox protein expression/function and how this affects immune cell function. We showed that 50% of carriers have an age-independent skewed-XCI and 65% of them have a misrepresented expression of the wild-type gene. The majority of carriers manifested immune dysregulation and GI manifestations regardless of age and XCI. Immunological investigations revealed an increase in CD19+ B cells, CD56bright-NK cell percentage, a slightly altered CD107a upregulation on CD4+ T cells, and reduced INFγ-production by CD4+ and CD8+ cells. Notably, we demonstrated that the residual level of ROS robustly correlates with INFγ-expressing T cells, suggesting a role in promoting immune dysregulation in carriers. MDPI 2021-06-01 /pmc/articles/PMC8229314/ /pubmed/34206017 http://dx.doi.org/10.3390/antiox10060891 Text en © 2021 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 Chiriaco, Maria Salfa, Irene Ursu, Giorgiana Madalina Cifaldi, Cristina Di Cesare, Silvia Rossi, Paolo Di Matteo, Gigliola Finocchi, Andrea Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers |
title | Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers |
title_full | Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers |
title_fullStr | Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers |
title_full_unstemmed | Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers |
title_short | Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers |
title_sort | immunological aspects of x-linked chronic granulomatous disease female carriers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229314/ https://www.ncbi.nlm.nih.gov/pubmed/34206017 http://dx.doi.org/10.3390/antiox10060891 |
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