Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers

Chiriaco, Maria and Salfa, Irene and Ursu, Giorgiana Madalina and Cifaldi, Cristina and Di Cesare, Silvia and Rossi, Paolo and Di Matteo, Gigliola and Finocchi, Andrea (2021) Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers. Antioxidants, 10 (6). p. 891. ISSN 2076-3921

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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.

Item Type: Article
Subjects: East India library > Agricultural and Food Science
Depositing User: Unnamed user with email support@eastindialibrary.com
Date Deposited: 17 Jul 2023 07:45
Last Modified: 28 May 2024 05:52
URI: http://info.paperdigitallibrary.com/id/eprint/1664

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