ArticleScientific reports2019
Mosaicism of XX and XXY cells accounts for high copy number of Toll like Receptor 7 and 8 genes in peripheral blood of men with Rheumatoid Arthritis.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Genes and Pathways Underpinning Klinefelter Syndrome at Bulk and Single-Cell Levels.Biochemical genetics · 2024Article
- Comprehensive Analysis of N6-Methyladenosine RNA Methylation Regulators in the Diagnosis and Subtype Classification of Rheumatoid Arthritis.Biochemical genetics · 2024Article
- Article
- Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives.Frontiers in immunology · 2023Review
- Regulation of the nucleic acid-sensing Toll-like receptors.Nature reviews. Immunology · 2022Review
- In Vitro Propagation of XXY Undifferentiated Mouse Spermatogonia: Model for Fertility Preservation in Klinefelter Syndrome Patients.International journal of molecular sciences · 2021Article
- Emerging epigenetic targets in rheumatoid arthritis.Rheumatology international · 2021Review
- Higher mortality of COVID-19 in males: sex differences in immune response and cardiovascular comorbidities.Cardiovascular research · 2020Review
- Nonendocrine mechanisms of sex bias in rheumatic diseases.Nature reviews. Rheumatology · 2019Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The X chromosome, hemizygous in males, contains numerous genes important to immunological and hormonal function. Alterations in X-linked gene dosage are suspected to contribute to female predominance in autoimmunity. A powerful example of X-linked dosage involvement comes from the BXSB murine lupus model, where the duplication of the X-linked Toll-Like Receptor 7 (Tlr7) gene aggravates autoimmunity in male mice. Such alterations are possible in men with autoimmune diseases. Here we showed that a quarter to a third of men with rheumatoid arthritis (RA) had significantly increased copy numbers (CN) of TLR7 gene and its paralog TLR8. Patients with high CN had an upregulated pro-inflammatory JNK/p38 signaling pathway. By fluorescence in situ hybridization, we further demonstrated that the increase in X-linked genes CN was due to the presence of an extra X chromosome in some cells. Men with RA had a significant cellular mosaicism of female (46,XX) and/or Klinefelter (47,XXY) cells among male (46,XY) cells, reaching up to 1.4% in peripheral blood. Our results present a new potential trigger for RA in men and opens a new field of investigation particularly relevant for gender-biased autoimmune diseases.
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