Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Systemic lupus erythematosus

Is X chromosome inactivation a cause or effect of SLE?

Nature Reviews Rheumatology volume 20, pages 599–600 (2024)Cite this article

Subjects

Autoimmune diseases such as systemic lupus erythematosus preferentially affect women, and multiple hypotheses are under investigation to elucidate this phenomenon. Emerging research suggests that multiple pathophysiological mechanisms and pathways are likely involved, including several that involve the X chromosome, but is skewing of X chromosome inactivation one of them?

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Conrad, N. et al. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. Lancet 401, 1878–1890 (2023).

    Article  PubMed  Google Scholar 

  2. Roberts, A. L. et al. Haematopoietic stem cell-derived immune cells have reduced X chromosome inactivation skewing in systemic lupus erythematosus. Ann. Rheum. Dis. https://doi.org/10.1136/ard-2024-225585 (2024).

  3. Scofield, R. H. et al. 47XXY and 47XXX in scleroderma and myositis. ACR Open Rheumatol 4, 528–533 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Shvetsova, E. et al. Skewed X-inactivation is common in the general female population. Eur. J. Hum. Genet. 27, 455–465 (2019).

    Article  CAS  PubMed  Google Scholar 

  5. Syrett, C. M. et al. Altered X-chromosome inactivation in T cells may promote sex-biased autoimmune diseases. JCI Insight https://doi.org/10.1172/jci.insight.126751 (2019).

  6. Broen, J. C. et al. Skewed X chromosomal inactivation impacts T regulatory cell function in systemic sclerosis. Ann. Rheum. Dis. 69, 2213–2216 (2010).

    Article  CAS  PubMed  Google Scholar 

  7. Ozcelik, T. et al. Evidence from autoimmune thyroiditis of skewed X-chromosome inactivation in female predisposition to autoimmunity. Eur. J. Hum. Genet. 14, 791–797 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Uz, E. et al. Increased frequency of extremely skewed X chromosome inactivation in juvenile idiopathic arthritis. Arthritis Rheum. 60, 3410–3412 (2009).

    Article  PubMed  Google Scholar 

  9. Huang, Q. et al. X-chromosome inactivation in monozygotic twins with systemic lupus erythematosus. Autoimmunity 26, 85–93 (1997).

    Article  CAS  PubMed  Google Scholar 

  10. Shaw, T. M. et al. X-linked genes exhibit miR6891-5p-regulated skewing in Sjögren’s syndrome. J. Mol. Med. https://doi.org/10.1007/s00109-022-02205-3 (2022).

Download references

Acknowledgements

The work of the authors is supported in part by US National Institutes of Health grants GM104938, AR053483 and AI1082714, and by US Department of Veterans Affairs award BX001451.

Author information

Authors and Affiliations

  1. Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    R. Hal Scofield & Valerie M. Lewis

  2. Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    R. Hal Scofield

  3. Research and Medical Services, Oklahoma City US Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA

    R. Hal Scofield & Valerie M. Lewis

Authors
  1. R. Hal Scofield
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valerie M. Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. Hal Scofield.

Ethics declarations

Competing interests

R.H.S. has received payment from Jensen Pharmaceuticals and Merck Pharmaceuticals for services performed as a member of advisory boards related to Sjögren’s disease, and holds grants from the US National Institutes of Health, the US Department of Veterans Affairs and the Sjögren’s Foundation. V.M.L. declares no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Scofield, R.H., Lewis, V.M. Is X chromosome inactivation a cause or effect of SLE?. Nat Rev Rheumatol 20, 599–600 (2024). https://doi.org/10.1038/s41584-024-01159-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41584-024-01159-9

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing