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. 2022 Dec;10(12):e2080.
doi: 10.1002/mgg3.2080. Epub 2022 Nov 9.

Evaluation of X chromosome inactivation in endemic Tunisian pemphigus foliaceus

Olfa Abida  1 , Nesrine Elloumi  1 , Emna Bahloul  2 , Hend Hachicha  1 , Khadija Sellami  2 , Raouia Fakhfakh  1 , Sameh Marzouk  3 , Ikhlas Ben Ayed  4 , Nadia Mahfoudh  5 , Hamida Turki  2 , Hatem Masmoudi  1
Affiliations

Evaluation of X chromosome inactivation in endemic Tunisian pemphigus foliaceus

Olfa Abida et al. Mol Genet Genomic Med. 2022 Dec.

Abstract

Background: Almost 5% of the world's population develops an autoimmune disease (AID), it is considered the fourth leading cause of disability for women, who represent 78% of cases. The sex ratio when it comes to the most prevalent AID varies from 9:1 in systemic lupus erythematosus (SLE) to 13:1 in endemic Tunisian pemphigus foliaceus (PF).

Methods: To test the potential involvement of skewed x-inactivation in the pathogenesis of Tunisian PF, we analyzed the methylation status of a highly polymorphic CAG repeat in the androgen receptor gene and evaluated the x chromosome inactivation (XCI) patterns in peripheral blood-leukocyte-derived DNA samples of female patients with PF (n = 98) compared to healthy control (HC) subjects (n = 150), as well as female patients with SLE (n = 98) were enrolled as a reference group.

Results: XCI status was informative for 50 of the 98 PF patients (51%) and 70 of the 150 HC women (47%). Extremely skewed XCI patterns were more frequent in PF and SLEwomen than HC, but the difference was statistically significant only in women with SLE. No statistical difference was observed in XCI patterns between PF and SLE patients. PF phenotype-XCI correlation analysis revealed that (i) skewed XCI patterns may be involved in the disease's subtype and (ii) it was more pronounced in the endemic group than the sporadic one. Furthermore, preferential XCI showed an increase in heterozygote genotypes of PF's susceptibility polymorphisms in immunity-related X genes (FOXP3, AR, and TLR7) in PF patients compared to HC.

Conclusion: Our results suggest that skewed XCI could lead to hemizygosity of X-linked alleles that might unmask X-linked deleterious alleles.

Keywords: X chromosome inactivation; autoimmune disease; pemphigus foliaceus.

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Conflict of interest statement

We declare having no conflicts of interest concerning published information in this study.

Figures

FIGURE 1
FIGURE 1
Flowchart for the inclusion and exclusion of the studied subjects. DIF: direct immunofluorescence, Dsg: desmoglein, IIF: indirect immunofluorescence.
See this image and copyright information in PMC

References

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