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Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers.

Authors :
Chiriaco M
Salfa I
Ursu GM
Cifaldi C
Di Cesare S
Rossi P
Di Matteo G
Finocchi A
Source :
Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2021 Jun 01; Vol. 10 (6). Date of Electronic Publication: 2021 Jun 01.
Publication Year :
2021

Abstract

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.

Details

Language :
English
ISSN :
2076-3921
Volume :
10
Issue :
6
Database :
MEDLINE
Journal :
Antioxidants (Basel, Switzerland)
Publication Type :
Academic Journal
Accession number :
34206017
Full Text :
https://doi.org/10.3390/antiox10060891